Estimation and projection of population lung cancer trends (United Kingdom).

OBJECTIVE: Reduction of overall cancer mortality in the UK will require a marked decrease in lung cancer incidence and mortality. A method was sought to predict future lung cancer trends at regional and subregional levels to improve planning, aid the monitoring of health promotion strategies, and to assess health gains that might be achieved. METHODS: Data on 55,000 lung cancer patients were used in an age-cohort model of lung cancer incidence (1981-95) and a parametric model of survival (1981-91). Indicators of deprivation were included in the models. Prevalence was estimated from the product of incidence and survival. Lung cancer trends were predicted to 2015, both at steady state and with an incidence perturbation. RESULTS: Female lung cancer is predicted to increase, until by 2015 the numbers will almost equal those in men. Cohort coefficients reveal an increasing risk of lung cancer in females born after 1941. Changing these female cohort coefficients to equate to a declining risk after 1941 suggests that, by 2015, around 200 cases per year might be prevented. This would necessitate a marked change in smoking behavior. Survival from lung cancer was significantly associated with social deprivation and health authority of residence. CONCLUSIONS: A credible model has been derived which can be used for health service and outcome monitoring. The model results have highlighted a priority area for smoking intervention which currently seems to attract little attention.

Analysis of incidence of childhood cancer in the West Midlands of the United Kingdom in relation to proximity to main roads and petrol stations.

OBJECTIVES: To investigate whether there is an excess of leukaemias in 0-15 year old children among those living in close proximity (within 100 m) of a main road or petrol station. METHODS: Data for 0-15 year old children diagnosed between 1990 and 1994 in the United Kingdom West Midlands were used. Postcode addresses were used to locate the point of residence which was compared with proximity to main roads and petrol stations separately, and to both together. Odds ratios (ORs) were calculated with solid tumours as a control, and incidence ratios (IRs) with population density as a control. RESULTS: The method based on solid tumours as a control showed ORs of 1.61 (95% confidence interval (95% CI) 0.90 to 2.87) and 1.99 (95% CI 0.73 to 5.43), for those living within 100 m of a main road or petrol station respectively. When population was used as a control, the estimated IRs for leukaemia were 1.16 (95% CI 0.74 to 1.72) and 1.48 (95% CI 0.65 to 2.93) for residence within 100 m of a main road or petrol station respectively, but neither reached significance at the 95% level. Results for residence in close proximity to both a main road and petrol station were inconsistent, but there were few. The influence of socioeconomic factors as represented by the Townsend deprivation index on leukaemia incidence was not significant and the results were not explicable on the basis of impact of social class. CONCLUSIONS: The results are suggestive of a small increase in risk of childhood leukaemia, but not solid tumours, for those living in close proximity to a main road or petrol station. This increase in risk is not, however, significant and a larger study is warranted to establish the true risk and causes of any increase in risk.

A pilot study using 99mTc to measure lead and platinum in the human kidney.

A pilot study has been conducted to investigate the hypothesis that the chemotherapeutic drug, cisplatinum, can mobilize skeletal lead. In vivo measurements of lead and platinum in the kidney of chemotherapy patients were performed with the technique of x-ray fluorescence, using 99mTc in a backscatter geometry. The results of the pilot study were inconclusive; the majority of patients exhibited no evidence of kidney lead at the level of system sensitivity, and negligible blood and urine lead levels.

In vivo measurements of lead in bone at four anatomical sites: long term occupational and consequent endogenous exposure.

Measurements of bone lead concentrations in the tibia, wrist, sternum, and calcaneus were performed in vivo by x ray fluorescence on active and retired lead workers from two acid battery factories, office personnel in the two factories under study, and control subjects. Altogether 171 persons were included. Lead concentrations in the tibia and ulna (representative of cortical bone) appeared to behave similarly with respect to time but the ulnar measurement was much less precise. In an analogous fashion, lead in the calcaneus and sternum (representative of trabecular bone) behaved in the same way, but sternal measurement was less precise. Groups occupationally exposed to lead were well separated from the office workers and the controls on the basis of calculated skeletal lead burdens, whereas the differences in blood lead concentrations were not as great, suggesting that the use of concentrations of lead in blood might seriously underestimate lead body burden. The exposures encountered in the study were modest, however. The mean blood lead value among active lead workers was 1.45 mumol l-1 and the mean tibial lead concentration 21.1 micrograms (g bone mineral)-1. The kinetics of lead in the tibia appeared to be noticeably different from that in the calcaneus. Tibial lead concentration increased consistently both as a function of intensity of exposure and of duration of exposure. Calcaneal lead concentration, by contrast, was strongly dependent on the intensity rather than duration of exposure. This indicated that the biological half life of lead in calcaneus was less than the seven to eight year periods into which the duration of exposure was split. Findings for retired workers clearly showed that endogenous exposure to lead arising from skeletal burdens accumulated over a working lifetime can easily produce the dominant contribution to systemic lead concentrations once occupational exposure has ceased.

Chelated lead and bone lead.

In this study a close correlation [correlation coefficient (r) = 0.86, P less than 0.001] was found between the blood lead level of 20 lead workers and their urinary excretion of lead for 24 h after intravenous infusion with 1 g of the chelating agent calcium disodium edetate. In addition, there were significant associations between lead levels in different bones (tibia/calcaneus: r = 0.93, P less than 0.001; tibia/phalanx: r = 0.67, P less than 0.002; calcaneus/phalanx: r = 0.80, P less than 0.001), as measured by in vivo X-ray fluorescence. Chelation produced no significant change in the lead level in either tibia or calcaneus. There was a significant correlation between chelated lead and bone lead (eg, for calcaneus, r = 0.62) in currently exposed workers. However, there was no significant relationship when a retired worker and an inactive worker were included (r = 0.14). It was concluded that chelatable lead mainly reflects the blood and soft-tissue lead pool, which is only partly dependent upon the skeletal lead content that comprises the biggest share of the total body burden.

Repeated measurements of tibia lead concentrations by in vivo x ray fluorescence in occupational exposure.

A group of workers occupationally exposed to lead have had measurements of their tibia lead concentrations made on two occasions separated by five years; on the second occasion calcaneus lead concentrations were also measured. The results serve to confirm the reliability of the measurement technique and to illustrate the improved precision achieved through technical improvements. More importantly, the relation between tibia lead concentration and cumulative blood lead found in this longitudinal study was entirely consistent with that previously reported, which had been based on cross sectional studies. Furthermore, the relation between lead concentrations in the tibia and in calcaneus found here was similar to that previously found in a larger cross sectional survey. It is concluded that this technique of measuring bone lead concentrations non-invasively is likely to be used increasingly as a biological monitor of cumulative exposure to lead.

Monte Carlo modelling of in vivo x-ray fluorescence of lead in the kidney.

A Monte Carlo program has been written to model the in vivo x-ray fluorescence of lead in the kidney, to aid the choice of one of four candidate fluorescing source/measurement geometry combinations: 109Cd/180 degrees, 57Co/90 degrees and 99Tcm at both 180 degrees and 90 degrees. Computational studies and practical considerations led to the choice of 99Tcm in a backscatter geometry for the measurement system.

Lead in bone: sampling and quantitation using K X-rays excited by 109Cd.

Lead in bone can be measured in vivo using gamma-rays from a 109Cd source to excite lead K X-rays. Normalization of lead X-ray amplitudes to that of the elastically backscattered 88 keV gamma-rays produces a determination of the concentration of lead in bone mineral that is accurate and insensitive to variations in measurement or bone geometry. For in vivo tibia measurements, a typical precision (1 SD) of +/- 5 micrograms lead (g bone mineral)-1 is achieved for an effective dose equivalent of 2.1 microSv. Measurement can be made of any superficial bone site, but precision will vary approximately as the inverse of the square root of the mass of bone mineral sampled. The apparatus required for this technique is readily transportable, and mobile laboratory facilities are easily established.

Effect of occupational lead exposure on serum 1,25-dihydroxyvitamin D levels.

The effects of lead exposure on serum 1,25-dihydroxyvitamin D levels and calcium homeostasis have been studied in 63 males occupationally exposed to the metal in the UK. The exposure indices used were blood lead, reflecting short-term exposure, and an in vivo X-ray fluorescence measurement of tibia lead which reflects cumulative lead exposure. Serum 1,25-dihydroxyvitamin D levels were higher than those in a referent population, who were non-occupationally exposed to lead, and were correlated with both blood lead and tibia lead. Multiple regression analysis suggested that blood lead was the variable responsible for the increase in serum 1,25-dihydroxyvitamin D. There were no other abnormalities in calcium metabolism associated with the degree of lead exposure.

In vivo measurements of bone lead--a comparison of two x-ray fluorescence techniques used at three different bone sites.

In vivo bone lead measurements have been made on a group of about 120 people, most of whom were lead exposed workers. Two different x-ray fluorescence (XRF) techniques were used to make measurements at three bone sites. Finger lead was measured using 57Co sources, and lead measurements were made in both tibia and calcaneus with a technique based on 109Cd sources. The results of the bone lead measurements correlated strongly with each other and with the index of cumulative exposure, thus confirming the value and reliability of these in vivo measurements as a tool in the study of chronic lead exposure. Measurement precision, +/- 1 standard deviation, was highest for tibia +/- 7.4 micrograms (g bone mineral)-1, +/- 16.6 micrograms (g bone mineral)-1 for the calcaneus and lowest for phalangeal lead +/- 25.0 micrograms (g bone mineral)-1. Maximum absorbed doses to the skin were comparable for all three measurements (1-3 mGy). The mean whole body dose equivalents were all low, but that for the finger measurement, 0.1 microSv, was significantly less than for the calcaneus and tibia measurements 3-5 microSv.

In vivo tibia lead measurements as an index of cumulative exposure in occupationally exposed subjects.

In vivo tibia lead measurements of 20 non-occupationally exposed and 190 occupationally exposed people drawn from three factories were made using a non-invasive x ray fluorescence technique in which characteristic x rays from lead are excited by gamma rays from a cadmium-109 source. The maximum skin dose to a small region of the shin was 0.45 mSv. The relation between tibia lead and blood lead was weak in workers from one factory (r = 0.11, p greater than 0.6) and among the non-occupationally exposed subjects (r = 0.07, p greater than 0.7); however, a stronger relation was observed in the other two factories (r = 0.45, p less than 0.0001 and r = 0.53, p less than 0.0001). Correlation coefficients between tibia lead and duration of employment were consistently higher at all three factories respectively (r = 0.86, p less than 0.0001; r = 0.61, p less than 0.0001; r = 0.80, p less than 0.0001). A strong relation was observed between tibia lead and a simple, time integrated, blood lead index among workers from the two factories from which blood lead histories were available. The regression equation from two groups of workers (n = 88, 79) did not significantly differ despite different exposure conditions. The correlation coefficient for the combined data set (n = 167) was 0.84 (p less than 0.0001). This shows clearly that tibia lead, measured in vivo by x-ray fluorescence, provides a good indicator of long term exposure to lead as assessed by a cumulative blood lead index.

In-vivo and in-vitro measurements of lead and cadmium.

Tibia lead is measured in vivo using X-ray fluorescence. A(109)Cd source is used to excite Pb K X-rays, and this signals is normalized to that from Rayleigh scattering to remove geometrical variations. The lower limit of detection is 10 µg/g for a mean absorbed dose, to the exposed section of the leg, of 100 µGy. Tibia lead correlated positively with age in normal volunteers (r=0.615,p=0.004) and with duration of exposure in occupationally exposed subjects (r=0.847,p=0.0001). When the X-ray fluorescence technique was applied to autopsy specimens previously analyzed by atomic absorption spectrometry there was excellent agreement between measurement techniques.Cadmium is measured in vivo by neutron activation analysis. The detection limit in liver is 6.5 µg/g for a local skin dose equivalent of 0.5 mSv and in kidney is 6.4 mg for a dose equivalent of 0.9 mSv to the skin. Detailed analysis of the γ-ray spectrum will produce only slight improvements in detection limit. Uncertainties in organ position during measurement, even after ultrasonic localization, are likely to produce uncertainties of 20-25% in cadmium measurement. Autopsy samples were measured, using a fast neutron activation method, from people previously measured in vivo. The results are broadly consistent, but show differences greater than those accounted for by counting statistics.

Comparison of two in vitro methods of bone lead analysis and the implications for in vivo measurements.

Atomic absorption spectrometry and x-ray fluorescence have been used to determine the lead content of metatarsal and tibia bone samples. For a range of bone lead levels from 6.5 to 83 micrograms g-1 of ashed bone there is no evidence of a systematic difference between the two techniques of more than 1 microgram g-1. There is, however, some evidence that random differences between the two in vitro analyses applied to the same bone sample are larger than can be accounted for by known measurement uncertainties. Variations in bone composition could account for these differences. Because the x-ray fluorescence technique is applied in an identical way to in vivo analysis, it is concluded that the uncertainties in in vivo measurements are small.

Unexpected mobilisation of lead during cisplatin chemotherapy.

During an investigation by X-ray fluorescence of platinum uptake in the kidney after chemotherapy with cisplatin, lead was found to have accumulated in the kidney in four subjects. The average kidney lead burden in one case exceeded 800 micrograms/g. Although two of the subjects had been occupationally exposed to lead, the other two had not. The tibia lead burden was also high in the two subjects in whom it was measured. The origins of this mobilised lead and the implications for cisplatin nephrotoxicity are discussed.

In vivo measurement of lead in bone using x-ray fluorescence.

The factors affecting the accuracy and minimum detectable concentration of in vivo tibia lead measurement are discussed, and it is demonstrated that the use of a 109Cd source in a backscatter geometry and using the 88 keV coherently scattered photon for normalisation optimizes both criteria. The measurement is shown to be independent of variations in source-sample distance, thickness of overlying tissue and tibia size and shape. Applying the same technique in vitro to samples of human tibia and metatarsals, it is shown that the results are not significantly different (p approximately equal to 0.9) from atomic absorption spectrometry results from another laboratory. The results of Monte Carlo dose distribution calculations are presented and compared with measurements using thermoluminescent dosemeters: the mean absorbed dose to a 20 cm leg section is less than 0.1 mGy (10 mrad) and the maximum absorbed skin dose is 0.45 mGy (45 mrad). For this dose the minimum detectable lead concentration is 10 micrograms g-1. Finally, the technique has been applied to groups of normals and occupationally exposed workers, and the means have been shown to be significantly different, namely 10 and 31 micrograms g-1 respectively. In the normal subjects tibia lead correlated strongly with age (r = 0.63, p less than 0.001).