Michael N. Bates

Increased mortality from lung cancer and bronchiectasis in young adults after exposure to arsenic in utero and in early childhood.

Arsenic in drinking water is an established cause of lung cancer, and preliminary evidence suggests that ingested arsenic may also cause nonmalignant lung disease. Antofagasta is the second largest city in Chile and had a distinct period of very high arsenic exposure that began in 1958 and lasted until 1971, when an arsenic removal plant was installed. This unique exposure scenario provides a rare opportunity to investigate the long-term mortality impact of early-life arsenic exposure. In this study, we compared mortality rates in Antofagasta in the period 1989–2000 with those of the rest of Chile, focusing on subjects who were born during or just before the peak exposure period and who were 30–49 years of age at the time of death. For the birth cohort born just before the high-exposure period (1950–1957) and exposed in early childhood, the standardized mortality ratio (SMR) for lung cancer was 7.0 [95% confidence interval (CI), 5.4–8.9; p < 0.001] and the SMR for bronchiectasis was 12.4 (95% CI, 3.3–31.7; p < 0.001). For those born during the high-exposure period (1958–1970) with probable exposure in utero and early childhood, the corresponding SMRs were 6.1 (95% CI, 3.5–9.9; p < 0.001) for lung cancer and 46.2 (95% CI, 21.1–87.7; p < 0.001) for bronchiectasis. These findings suggest that exposure to arsenic in drinking water during early childhood or in utero has pronounced pulmonary effects, greatly increasing subsequent mortality in young adults from both malignant and nonmalignant lung disease.

Campylobacteriosis in New Zealand: results of a case-control study.

STUDY OBJECTIVE: To identify and assess the contributions of major risk factors for campylobacteriosis in New Zealand. DESIGN: Case-control study. Home interviews were conducted over nine months using a standardised questionnaire to assess recent food consumption and other exposures. SETTING: Four centres in New Zealand with high notification rates of campylobacter infections--Auckland, Hamilton, Wellington, and Christchurch. PARTICIPANTS: Case patients were 621 people notified between 1 June 1994 and 28 February 1995 as having campylobacter infection. Control subjects were selected randomly from telephone directories, and were matched 1:1 with case patients in relation to sex, age group, and home telephone prefix. RESULTS: Risk of campylobacteriosis was strongly associated with recent consumption of raw or undercooked chicken (matched odds ratio 4.52, 95% confidence interval 2.88, 7.10). There was also an increased risk with chicken eaten in restaurants (matched odds ratio 3.85; 2.52, 5.88). Recent consumption of baked or roasted chicken seemed to be protective. Campylobacteriosis was also associated with recent overseas travel, rainwater as a source of water at home, consumption of raw dairy products, and contact with puppies and cattle, particularly calves. CONCLUSIONS: Improperly cooked chicken seems to be associated with a large proportion of campylobacteriosis in New Zealand. Thorough cooking of chicken in homes and restaurants could reduce considerably the incidence of this disease.

Respiratory risks from household air pollution in low and middle income countries

A third of the worlds population uses solid fuel derived from plant material (biomass) or coal for cooking, heating, or lighting. These fuels are smoky, often used in an open fire or simple stove with incomplete combustion, and result in a large amount of household air pollution when smoke is poorly vented. Air pollution is the biggest environmental cause of death worldwide, with household air pollution accounting for about 3·5-4 million deaths every year. Women and children living in severe poverty have the greatest exposures to household air pollution. In this Commission, we review evidence for the association between household air pollution and respiratory infections, respiratory tract cancers, and chronic lung diseases. Respiratory infections (comprising both upper and lower respiratory tract infections with viruses, bacteria, and mycobacteria) have all been associated with exposure to household air pollution. Respiratory tract cancers, including both nasopharyngeal cancer and lung cancer, are strongly associated with pollution from coal burning and further data are needed about other solid fuels. Chronic lung diseases, including chronic obstructive pulmonary disease and bronchiectasis in women, are associated with solid fuel use for cooking, and the damaging effects of exposure to household air pollution in early life on lung development are yet to be fully described. We also review appropriate ways to measure exposure to household air pollution, as well as study design issues and potential effective interventions to prevent these disease burdens. Measurement of household air pollution needs individual, rather than fixed in place, monitoring because exposure varies by age, gender, location, and household role. Women and children are particularly susceptible to the toxic effects of pollution and are exposed to the highest concentrations. Interventions should target these high-risk groups and be of sufficient quality to make the air clean. To make clean energy available to all people is the long-term goal, with an intermediate solution being to make available energy that is clean enough to have a health impact.

Arsenic Methylation and Bladder Cancer Risk in Case-Control Studies in Argentina and the United States

Objective: We sought to assess whether the metabolism of arsenic impacts a persons susceptibility to bladder cancer. Methods: Urinary methylation products were measured in subjects from Argentina (114 cases and 114 controls) and the United States (23 cases and 49 controls). Results: In Argentina, the adjusted odds ratio (OR) for subjects with a high proportion of ingested arsenic excreted as monomethylarsonate (%MMA) was 2.17 (95% confidence interval [CI] = 1.02–4.63) in smokers and 0.48 (95% CI = 0.17–1.33) in nonsmokers. In the United States, the adjusted ORs for high %MMA in subjects with arsenic intakes less than and greater than 100 &mgr;g/d were 1.20 (95% CI = 0.27–5.38) and 2.70 (95% CI = 0.39–18.6). Conclusions: Overall, these results are consistent with data from Taiwan suggesting that some individuals who excrete a higher proportion of ingested arsenic as MMA are more susceptible to arsenic-related cancer.

Kerosene: a review of household uses and their hazards in low- and middle-income countries

Kerosene has been an important household fuel since the mid-19th century. In developed countries its use has greatly declined because of electrification. However, in developing countries, kerosene use for cooking and lighting remains widespread. This review focuses on household kerosene uses, mainly in developing countries, their associated emissions, and their hazards. Kerosene is often advocated as a cleaner alternative to solid fuels, biomass and coal, for cooking, and kerosene lamps are frequently used when electricity is unavailable. Globally, an estimated 500 million households still use fuels, particularly kerosene, for lighting. However, there are few studies, study designs and quality are varied, and results are inconsistent. Well-documented kerosene hazards are poisonings, fires, and explosions. Less investigated are exposures to and risks from kerosenes combustion products. Some kerosene-using devices emit substantial amounts of fine particulates, carbon monoxide (CO), nitric oxides (NOx), and sulfur dioxide (SO2). Studies of kerosene used for cooking or lighting provide some evidence that emissions may impair lung function and increase infectious illness (including tuberculosis), asthma, and cancer risks. However, there are few study designs, quality is varied, and results are inconsistent. Considering the widespread use in the developing world of kerosene, the scarcity of adequate epidemiologic investigations, the potential for harm, and the implications for national energy policies, researchers are strongly encouraged to consider collecting data on household kerosene uses in studies of health in developing countries. Given the potential risks of kerosene, policymakers may consider alternatives to kerosene subsidies, such as shifting support to cleaner technologies for lighting and cooking.

Comparison of pulmonary and extrapulmonary tuberculosis in Nepal- a hospital-based retrospective study

BackgroundStudies from developed countries have reported on host-related risk factors for extra-pulmonary tuberculosis (EPTB). However, similar studies from high-burden countries like Nepal are lacking. Therefore, we carried out this study to compare demographic, life-style and clinical characteristics between EPTB and PTB patients.MethodsA retrospective analysis was carried out on 474 Tuberculosis (TB) patients diagnosed in a tertiary care hospital in western Nepal. Characteristics of demography, life-style and clinical features were obtained from medical case records. Risk factors for being an EPTB patient relative to a PTB patient were identified using logistic regression analysis.ResultsThe age distribution of the TB patients had a bimodal distribution. The male to female ratio for PTB was 2.29. EPTB was more common at younger ages (< 25 years) and in females. Common sites for EPTB were lymph nodes (42.6%) and peritoneum and/or intestines (14.8%). By logistic regression analysis, age less than 25 years (OR 2.11 95% CI 1.12–3.68) and female gender (OR 1.69, 95% CI 1.12–2.56) were associated with EPTB. Smoking, use of immunosuppressive drugs/steroids, diabetes and past history of TB were more likely to be associated with PTB.ConclusionResults suggest that younger age and female gender may be independent risk factors for EPTB in a high-burden country like Nepal. TB control programmes may target young and female populations for EPTB case-finding. Further studies are necessary in other high-burden countries to confirm our findings.

Individual differences in arsenic metabolism and lung cancer in a case-control study in Cordoba, Argentina

In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although in most people this process is not complete. Previous studies have identified associations between the proportion of urinary MMA (%MMA) and increased risks of several arsenic-related diseases, although none of these reported on lung cancer. In this study, urinary arsenic metabolites were assessed in 45 lung cancer cases and 75 controls from arsenic-exposed areas in Cordoba, Argentina. Folate has also been linked to arsenic-disease susceptibility, thus an exploratory assessment of associations between single nucleotide polymorphisms in folate metabolizing genes, arsenic methylation, and lung cancer was also conducted. In analyses limited to subjects with metabolite concentrations above detection limits, the mean %MMA was higher in cases than in controls (17.5% versus 14.3%, p=0.01). The lung cancer odds ratio for subjects with %MMA in the upper tertile compared to those in the lowest tertile was 3.09 (95% CI, 1.08-8.81). Although the study size was too small for a definitive conclusion, there was an indication that lung cancer risks might be highest in those with a high %MMA who also carried cystathionine beta-synthase (CBS) rs234709 and rs4920037 variant alleles. This study is the first to report an association between individual differences in arsenic metabolism and lung cancer, a leading cause of arsenic-related mortality. These results add to the increasing body of evidence that variation in arsenic metabolism plays an important role in arsenic-disease susceptibility.

Confidence limit analyses should replace power calculations in the interpretation of epidemiologic studies.

Frequently, after an epidemiologic study is completed, statistical power to detect a relative risk of interest is recalculated using data obtained during the course of the study. A negative study may then be dismissed on the grounds that its power was too low. However, post hoc power calculations ignore the actual relative estimate and its variance, which are by then known. We present evidence that post-study power calculations have little value and should be replaced by a more informative method using the upper (1 - alpha)% confidence limit of the point estimate that touches the value of the relative risk of interest.

Genetic Polymorphisms in MTHFR 677 and 1298, GSTM1 and T1, and Metabolism of Arsenic

Methylation is the primary route of metabolism of inorganic arsenic in humans, and previous studies showed that interindividual differences in arsenic methylation may have important impacts on susceptibility to arsenic-induced cancer. To date, the factors that regulate arsenic methylation in humans are mostly unknown. Urinary arsenic methylation patterns and genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and glutathione S-transferase (GST) were investigated in 170 subjects from an arsenic-exposed region in Argentina. Previous studies showed that subjects with the TT/AA polymorphisms at MTHFR 677 and 1298 have lower MTHFR activity than others. In this study, it was found that subjects with the TT/AA variant of MTHFR 677/1298 excreted a significantly higher proportion of ingested arsenic as inorganic arsenic and a lower proportion as dimethylarsinic acid. Women with the null genotype of GSTM1 excreted a significantly higher proportion of arsenic as monomethylarsonate than women with the active genotype. No associations were seen between polymorphisms in GSTT1 and arsenic methylation. This is the first study to report (1) associations between MTHFR and arsenic metabolism in humans, and (2) gender differences between genetic polymorphisms and urinary arsenic methylation patterns. Overall, this study provides evidence that MTHFR and GSTM1 are involved in arsenic metabolism in humans, and polymorphisms in the genes that encode these enzymes may play a role in susceptibility to arsenic-induced cancer.

Tuberculosis and Indoor Biomass and Kerosene Use in Nepal: A Case–Control Study

Background In Nepal, tuberculosis (TB) is a major problem. Worldwide, six previous epidemiologic studies have investigated whether indoor cooking with biomass fuel such as wood or agricultural wastes is associated with TB with inconsistent results. Objectives Using detailed information on potential confounders, we investigated the associations between TB and the use of biomass and kerosene fuels. Methods A hospital-based case–control study was conducted in Pokhara, Nepal. Cases (n = 125) were women, 20–65 years old, with a confirmed diagnosis of TB. Age-matched controls (n = 250) were female patients without TB. Detailed exposure histories were collected with a standardized questionnaire. Results Compared with using a clean-burning fuel stove (liquefied petroleum gas, biogas), the adjusted odds ratio (OR) for using a biomass-fuel stove was 1.21 [95% confidence interval (CI), 0.48–3.05], whereas use of a kerosene-fuel stove had an OR of 3.36 (95% CI, 1.01–11.22). The OR for use of biomass fuel for heating was 3.45 (95% CI, 1.44–8.27) and for use of kerosene lamps for lighting was 9.43 (95% CI, 1.45–61.32). Conclusions This study provides evidence that the use of indoor biomass fuel, particularly as a source of heating, is associated with TB in women. It also provides the first evidence that using kerosene stoves and wick lamps is associated with TB. These associations require confirmation in other studies. If using kerosene lamps is a risk factor for TB, it would provide strong justification for promoting clean lighting sources, such as solar lamps.