Michael C. R. Alavanja

Passive smoking and lung cancer in nonsmoking women

OBJECTIVESnThe causes of lung cancer among nonsmokers are not clearly understood. To further evaluate the relation between passive smoke exposure and lung cancer in nonsmoking women, we conducted a population-based, case-control study.nnnMETHODSnCase patients (n = 618), identified through the Missouri Cancer Registry for the period 1986 through 1991, included 432 lifetime nonsmokers and 186 ex-smokers who had stopped at least 15 years before diagnosis or who had smoked for less than 1 pack-year. Control subjects (n = 1402) were selected from drivers license and Medicare files.nnnRESULTSnNo increased risk of lung cancer was associated with childhood passive smoke exposure. Adulthood analyses showed an increased lung cancer risk for lifetime nonsmokers with exposure of more than 40 pack-years from all household members (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0, 1.8) or from spouses only (OR = 1.3; 95% CI = 1.0, 1.7). When the time-weighted product of pack-years and average hours exposed per day was considered, a 30% excess risk was shown at the highest quartile of exposure among lifetime nonsmokers.nnnCONCLUSIONSnOurs and other recent studies suggest a small but consistent increased risk of lung cancer from passive smoking. Comprehensive actions to limit smoking in public places and worksites are well-advised.

The Validation of a Pesticide Exposure Algorithm Using Biological Monitoring Results

A pesticide exposure algorithm was developed to calculate pesticide exposure intensity scores based on responses to questions about pesticide handling procedures and application methods in a self-administered questionnaire. The validity of the algorithm was evaluated through comparison of the algorithm scores with biological monitoring data from a study of 126 pesticide applicators who applied the herbicdes MCPA or 2,4-D. The variability in the algorithm scores calculated for these applicators was due primarily to differences in their use of personal protective equipment (PPE). Rubber gloves were worn by 75% of applicators when mixing and 22% when applying pesticides, rubber boots were worn by 33% when mixing and 23% when applying, and goggles were worn by 33% and 17% of applicators when mixing and when applying, respectively. Only 2% of applicators wore all three types of PPE when both mixing and applying, and 15% wore none of these three types of PPE when either mixing or applying. Substantial variability was also observed in the concentrations of pesticides detected in the post application urine samples. The concentration of MCPA detected in urine samples collected on the second day after the application ranged from less than < 1.0 to 610 μg/L among 84 of the applicators who applied MCPA. The concentrations of 2,4-D detected in the urine samples ranged from less than < 1.0 to 514 μg/L among 41 of the applicators who applied 2,4-D. When categorized into three groups based on the algorithm scores, the geometric mean in the highest exposure group was 20 μg/L compared with 5 μg/L in the lowest exposure group for the MCPA applicators, and 29 μg/L in highest exposure group compared with 2 μg/L in the low exposure group for the 2,4-D applicators. A regression analysis detected statistically significant trends in the geometric mean of the urine concentrations across the exposure categories for both the 2,4-D and the MCPA applicators. The algorithm scores, based primarily on the use of PPE, appear to provide a reasonably valid measure of exposure intensity for these applicators, however, further studies are needed to generalize these results to other types of pesticides and application methods.

Animal production and wheeze in the Agricultural Health Study: interactions with atopy, asthma, and smoking

Background: Exposure to animals, their feeds, and by-products contribute to respiratory symptoms among farmers. Aims: To investigate the role of animal exposures and wheeze, and to assess whether their impact differs among susceptible subgroups, including atopics, asthmatics, and smokers. Methods: Using the Agricultural Health Study, a cohort of pesticide applicators in Iowa and North Carolina enrolled in 1994–97, wheeze associated with animal production was evaluated and interactions among susceptible subgroups assessed. Logistic regression models were used to examine risk factors for wheeze in the past year among 20 468 farmers. Results: Individuals raising animals requiring direct contact had the highest odds ratios (OR) for wheeze (ORdairy = 1.26; OReggs = 1.70). A significant dose response was observed for both the number of poultry and the number of livestock on the farm. Farmers who performed veterinary procedures on a daily basis had an OR of 1.51. The odds of wheeze associated with poultry production was greater among atopic than non-atopic individuals. Milking cows daily increased the odds of wheeze in all individuals, with the largest association observed among atopic asthmatic individuals. The impact of dairy, poultry, and egg production varied among smoking groups. Past smokers had the highest odds ratios, followed by never smokers, and then current smokers. The OReggs was 2.88 among past smokers but only 1.46 for never smokers. The OReggs for current smokers of 0.80 might reflect self selection of exposure among smokers. Conclusions: Results are consistent with animal production and respiratory symptoms, and suggest that subgroups may respond differently to exposure.

Pesticides and adult respiratory outcomes in the agricultural health study

Abstract:u2002 In the 1700s, Bernardino Ramazzini was among the first to describe respiratory disease among agricultural workers. Since then, farmers continue to have higher rates of respiratory illnesses, even as changes occur in occupational and environmental exposures on farms. While grain and animal exposures have been well studied for their role in agricultural lung diseases, pesticide exposures have not. Using the Agricultural Health Study, a prospective cohort study of ∼89,000 licensed pesticide applicators and their spouses in Iowa and North Carolina, we are currently assessing the association of pesticides with respiratory outcomes, including wheeze, adult asthma, farmers lung, and chronic bronchitis. At enrollment (1993–1997), 19% of farmers and 22% of commercial pesticide applicators reported wheeze in the previous year. Using logistic regression models adjusted for age, state, smoking status, and body mass index, we evaluated the association of 40 individual pesticides with wheeze within these two groups separately. In both groups, we observed strong evidence of an association of organophosphates with wheeze. For farmers, the organophosphates chlorpyrifos, malathion, and parathion were positively associated with wheeze; for the commercial applicators, the organophosphates chlorpyrifos, dichlorvos, and phorate were positively associated with wheeze. Chlorpyrifos was strongly associated with wheeze in a dose‐dependent manner in both groups; use of chlorpyrifos for at least 20 days per year had an odds ratio of 1.48 (95% confidence interval [CI]= 1.00–2.19) for farmers and 1.96 (95% CI = 1.05–3.66) for commercial applicators. Our wheeze results are consistent with recent animal models that support a role for organophosphates and respiratory outcomes.

Estimating past exposure to indoor radon from household glass

CR-39 plastic was attached to household glass objects to learn whether residual radioactivity from radon decay products could be measured and correlated with cumulative radon exposures over defined time periods. Such an approach could be used to increase the completeness of exposure data collected in epidemiologic studies of residential radon. Inability to estimate radon concentrations for all residences adversely effects statistical power and thus the ability to detect an effect of radon exposure on lung cancer risk. A feasibility study was performed to determine if affixing CR-39 surface monitors to selected glass, ceramic, or enameled objects provided comparable estimates of past residential radon exposure to those obtained from year-long ambient alpha track-etch measurements. The CR-39 measurements of alpha activity in the surface of selected objects correlated with ambient radon measurements (R2 = 0.48) provided that reliable information was obtained on the history and age of the objects. This technique has now been incorporated into an epidemiologic study of radon and lung cancer to more fully estimate past exposure to indoor radon.

Respiratory disease in United States farmers

Objectives Farmers may be at increased risk for adverse respiratory outcomes compared with the general population due to their regular exposures to dusts, animals and chemicals. However, early life farm exposures to microbial agents may result in reduced risk. Understanding respiratory disease risk among farmers and identifying differences between farmers and other populations may lead to better understanding of the contribution of environmental exposures to respiratory disease risk in the general population. Methods We compared the prevalence of self-reported respiratory outcomes in 43548 participants from the Agricultural Health Study (AHS), a prospective cohort of farmers and their spouses from Iowa and North Carolina, with data from adult participants in the National Health and Nutrition Examination Survey (NHANES) over the same period (2005–2010). Results AHS participants had lower prevalences of respiratory diseases (asthma, adult-onset asthma, chronic bronchitis and emphysema), but higher prevalences of current respiratory symptoms (wheeze, cough and phlegm) even after controlling for smoking, body mass index and population characteristics. The overall prevalence of asthma in the AHS (7.2%, 95% CI 6.9 to 7.4) was 52% of that in NHANES (13.8%, 95% CI 13.3 to 14.3), although the prevalence of adult-onset asthma among men did not differ (3.6% for AHS, 3.7% for NHANES). Conversely, many respiratory symptoms were more common in the AHS than NHANES, particularly among men. Conclusions These findings suggest that farmers and their spouses have lower risk for adult-onset respiratory diseases compared with the general population, and potentially higher respiratory irritation as evidenced by increased respiratory symptoms.

Radon, secondhand smoke, glutathione-S-transferase M1 and lung cancer among women

Tobacco smoke and ionizing radiation induce oxidative stress by transmitting or generating reactive oxygen species (ROS). We hypothesized that glutathione‐S‐transferase M1 (GSTM1) null homozygotes would have decreased ability to neutralize ROS that might increase their susceptibility to lung cancer. A case‐only design was used with lung cancer cases pooled from 3 previously completed case‐control studies using archival tissue samples from 270 lung cancer cases to genotype GSTM1. Radon concentrations were measured with long‐term α‐track radon detectors. Secondhand smoke (SHS) was measured with questionnaires and interviews. Unconditional logistic regression was used to calculate the interaction odds ratios (OR) and 95% confidence intervals (95% CI). Radon concentrations >121 Bq m−3 were associated with a >3‐fold interaction OR (OR = 3.41; 95% CI = 1.10, 10.61) for GSTM1 null homozygotes compared to GSTM1 carriers; the linear trend was significant (p trend = 0.03). The SHS and GSTM1 interaction OR was also elevated (OR = 2.28; 95% CI = 1.15–4.51) among never‐smokers. This may be the first study to provide evidence of a GSTM1 and radon interaction in risk of lung cancer. Additionally, these findings support the hypothesis that radon and SHS promote neoplasia through shared elements of a common pathway.

Mortality among Forest and Soil Conservationists

The mortality of forest conservationists and soil conservationists in the United States Department of Agriculture (USDA) who died during January 1, 1970-December 31, 1979 (N = 1,411 white males) while actively employed or while receiving a pension was evaluated. The proportionate mortality analysis was used to identify cancers that might be elevated in this occupational group compared to the total U.S. white male population, whereas case-control analyses more rigorously evaluated the disease association with occupation. Controls were selected from employees at USDA who died of any cause of death other than that cause of death represented by the case. In case-control analyses, non-Hodgkins lymphoma (NHL) and colon cancer demonstrated a statistically significant linear trend (p less than .05) with duration of employment as either a forest or soil conservationist, which suggests an occupational etiology for both diseases. Soil conservationists who were last employed after 1960 experienced significantly elevated risks for NHL (OR = 2.6) and colon cancer (OR = 1.8), whereas those last employed before 1960 were not at an increased risk. Among forest conservationists, the risk for both NHL and colon cancer appeared to be elevated before and after 1960.

Pesticides are Associated with Allergic and Non-Allergic Wheeze among Male Farmers

Background: Growing evidence suggests that pesticide use may contribute to respiratory symptoms. Objective: We evaluated the association of currently used pesticides with allergic and non-allergic wheeze among male farmers. Methods: Using the 2005–2010 interview data of the Agricultural Health Study, a prospective study of farmers in North Carolina and Iowa, we evaluated the association between allergic and non-allergic wheeze and self-reported use of 78 specific pesticides, reported by ≥ 1% of the 22,134 men interviewed. We used polytomous regression models adjusted for age, BMI, state, smoking, and current asthma, as well as for days applying pesticides and days driving diesel tractors. We defined allergic wheeze as reporting both wheeze and doctor-diagnosed hay fever (n = 1,310, 6%) and non-allergic wheeze as reporting wheeze but not hay fever (n = 3,939, 18%); men without wheeze were the referent. Results: In models evaluating current use of specific pesticides, 19 pesticides were significantly associated (p < 0.05) with allergic wheeze (18 positive, 1 negative) and 21 pesticides with non-allergic wheeze (19 positive, 2 negative); 11 pesticides were associated with both. Seven pesticides (herbicides: 2,4-D and simazine; insecticides: carbaryl, dimethoate, disulfoton, and zeta-cypermethrin; and fungicide pyraclostrobin) had significantly different associations for allergic and non-allergic wheeze. In exposure–response models with up to five exposure categories, we saw evidence of an exposure–response relationship for several pesticides including the commonly used herbicides 2,4-D and glyphosate, the insecticides permethrin and carbaryl, and the rodenticide warfarin. Conclusions: These results for farmers implicate several pesticides that are commonly used in agricultural and residential settings with adverse respiratory effects. Citation: Hoppin JA, Umbach DM, Long S, London SJ, Henneberger PK, Blair A, Alavanja M, Beane Freeman LE, Sandler DP. 2017. Pesticides are associated with allergic and non-allergic wheeze among male farmers. Environ Health Perspect 125:535–543;u2002http://dx.doi.org/10.1289/EHP315

Pesticide use and fatal injury among farmers in the Agricultural Health Study

PurposeTo assess whether pesticide use practices were associated with injury mortality among 51,035 male farmers from NC and IA enrolled in the Agricultural Health Study.MethodsWe used Cox proportional hazards models adjusted for age and state to estimate fatal injury risk associated with self-reported use of 49 specific pesticides, personal protective equipment, specific types of farm machinery, and other farm factors collected 1–15xa0years preceding death. Cause-specific mortality was obtained through linkage to mortality registries.ResultsWe observed 338 injury fatalities over 727,543 person-years of follow-up (1993–2008). Fatal injuries increased with days/year of pesticide application, with the highest risk among those with 60+ days of pesticide application annually [hazard ratio (HR)xa0=xa01.87; 95% confidence interval (CI)xa0=xa01.10, 3.18]. Chemical-resistant glove use was associated with decreased risk (HRxa0=xa00.73; 95% CIxa0=xa00.58, 0.93), but adjusting for glove use did not substantially change estimates for individual pesticides or pesticide use overall. Herbicides were associated with fatal injury, even after adjusting for operating farm equipment, which was independently associated with fatal injury. Ever use of five of 18 herbicides (2,4,5-T, paraquat, alachlor, metribuzin, and butylate) were associated with elevated risk. In addition, 2,4-D and cyanazine were associated with fatal injury in exposure–response analyses. There was no evidence of confounding of these results by other herbicides.ConclusionThe association between application of pesticides, particularly certain herbicides, and fatal injuries among farmers should be interpreted cautiously but deserves further evaluation, with particular focus on understanding timing of pesticide use and fatal injury.