There also may be some degree of misclassification of smoker status, as the diagnosis of recent exposure to cigarette smoke was based on the presence of clusters of characteristic smoker’s macrophages in the alveoli adjacent to the respiratory bronchioles. Although not well documented for humans, it is likely that high and prolonged exposure to diesel emissions or burning biomass could produce similar changes in the lung. These types of exposures are relatively common in the farming industry. Misclassification of smoking status would not affect the relationships we saw between agricultural work, mineral dust in the lung, mineral dust small airway disease, and pneumoconiosis. The statistically significant association of smoking with reduced odds of mineral dust small airways disease is of unknown significance. Cigarette smoking was associated with increased odds for other respiratory health outcomes, as expected. Examination of Figure 3 shows that farm work and smoking have additive effects on the milder grades of small airway fibrosis. However the data also indicate that there is a maximal response to these agents that might account for the negative interaction in the multivariate analyses. Morbidity and mortality studies in several countries have observed an association of COPD and agricultural work , but this is not observed in all agricultural populations . This association is observed concomitant with a lower mortality rate from lung cancer, reflecting the lower known smoking prevalence among agricultural workers . We observed a strong association of mineral dust exposure with interstitial fibrosis and pneumoconiosis, after adjustment for cigarette smoking. However, we also found independent associations of mineral dust exposure and emphysema, chronic bronchitis,hydroponic net pots lymph node fibrosis, and mineral dust small airways disease.
Our findings suggest one possible mechanism for a causal association of agricultural work and COPD: exposure to elevated mineral dust levels. We have previously documented very high occupational exposures to respirable particles among agricultural workers in California’s central valley . For example, personal dust exposure levels measured during various operations such as land planning and disking yielded geometric mean particle concentrations of 57.3 and 98.6 mg/m3, respectively. Although these samples were weighted toward large particles, respirable particle concentrations of 1‒3 mg/m3 were nevertheless common. Situated in the heart of the San Joaquin Valley, Fresno has some of the highest ambient inhalable particle concentrations in the United States, often exceeding the National Ambient Air Quality Standard of 150 µg/m3 averaged over 24 hr . Chow et al. describe in detail the physicochemical characteristics and seasonal variability of PM in Fresno. During the winter months, the highest PM10 concentrations have a dominant PM2.5 fraction . These particles consist mostly of carbonaceous constituents as well as ammonium nitrate and sulfate . Elevated PM10 concentrations during the summer and early fall occur because of windblown dust excursions, which have been found most often in the southern San Joaquin Valley and in the high desert regions. These situations are dominated by fugitive dusts, mostly associated with coarse particles. From 14 June 1994 through 9 June 1995, when the autopsy material was collected for this study, California and federal 24-hr and annual standards for PM10 were regularly exceeded in Fresno County at both urban and non urban sites . During this time, the PM10 daily average concentration in Fresno was 43.5 µg/m3, and the maximum 24-hr PM10 concentration was 122 µg/m3. The corresponding levels of PM2.5 were 22 and 65 µg/m3. Oxidant gases were also measured during this period. One-hour measurements of nitrogen oxides averaged 0.109 ppm, with maximal levels reaching 0.7 ppm.
The average 1-hr concentration of ozone during this time was 0.06 ppm, whereas the maximum 1-hr ozone concentration was 0.17 ppm. Sulfur oxide levels averaged 0.0054 ppm with a maximal concentration of 0.017 ppm . In a previous study involving a subset of this population, we used a systematic approach to determine the distribution of ambient particles in the human lung and their potential role in tissue remodeling . This approach involved dissection of defined airway paths and parenchymal sampling in adjacent regions. As a result of this sampling procedure, the importance of terminal and respiratory bronchioles as sites for particle retention and the association of particle retention with subtle but quantifiable changes in tissue remodeling were clearly established. The importance of this site as a target for particleinduced injury is well established in occupational settings . The centriacinar region is the primary site of injury in coal worker’s pneumoconiosis , asbestosis-induced injury , and silica- and silicate-induced injury .Cigarette smoking and highly polluted urban centers also induce injury in this region, and there is considerable evidence that respiratory bronchiolitis precedes the functionally more important disease of centriacinar emphysema by several decades . However, it is not generally recognized that subtle lesions can occur in the centriacinar zone of the lung in individuals exposed to ambient particles. Our results show a continuum of changes in the respiratory and membranous bronchioles, being most severe in individuals who smoke and in persons exposed to agricultural dusts, but also present to a lesser degree in the population in general. The latter is not surprising in view of the poor air quality in the region . We do not have data on lifetime exposures, but both the agricultural workers and non-agricultural workers would likely have had similar exposure to ambient air pollutants.
The high levels of ozone in this region may also be contributing to the background levels of airway disease . The physiologic effects of the small airway lesions are uncertain, because subtle changes such as those shown in this study can be detected only by nonroutine tests for small airway function . However, the changes described here in these young farm workers may not be trivial, as they can progress to clinically significant disease . Pyrethroids are the most commonly utilized residential insecticides partly due to the generally held belief that they pose minimal risk to human health. In addition, there are numerous worldwide applications for pyrethroids in agriculture, horticulture, public health and textiles . They have insecticidal activity in their parent form and donot require metabolic activation to exert their neurotoxic effects, which are mediated by increased open time of voltage-gated sodium channels . The initial symptoms of acute occupational pyrethroid intoxication include parasthesia consisting of burning and itching sensations on the skin or dizziness that develops approximately 4–6 h after exposure, although dermal symptoms can manifest after minutes of application. Systemic symptoms can occur up to 48 h after acute exposure . Pyrethroids are classified as Type I or Type II pyrethroids. Type I pyrethroids are esters of primary or secondary alcohols,blueberry grow pot whereas Type II pyrethroids are esters of secondary alcohols with a cyano group at the -carbon of the alcohol component. The acid andalcohol moieties both contain chiral centers, leading to the possibility of several stereoisomers for each pyrethroid, which may exhibit isomer-specific insecticidal activity . The type II pyrethroid, CM, is derived from the 8- stereoisomers that comprise the pyrethroid cypermethrin, which is one of the most common pyrethroids in agricultural and residential use. CM is a racemate of two cypermethrin stereoisomers: – -cyano-3-phenoxybenzyl–cis-3–2,2-dimethylcyclopropane carboxylate, and – -cyano-3-phenoxybenzyl–cis-3– 2,2-dimethylcyclopropane carboxylate , which are considered the two most stable cis-isomers . The major detoxification pathway of CM is through hydrolysis by esterases and hydroxylation by cytochrome P450s . In vitro studies have shown that alcohol and aldehyde dehydrogenases can also contribute to the metabolism of pyrethroids . Dosing studies with CM and cypermethrin in 6 human volunteers indicate an elimination half-life range of 8–22 h for a single dermal exposure .
The assessment of human exposure to insecticides such as pyrethroids is often based on quantification of metabolites excreted in urine . The major urinary metabolites of CM in humans are 3-phenoxybenzoic acid and cis-3–2,2-dimethylcyclopropane carboxylic acid , which are conjugated prior to being excreted in the urine . 3-PBA is a metabolite common to a large number of pyrethroid insecticides, while cisDCCA is a more specific metabolite and useful urinary biomarker of exposure for CM, permethrin and cyfluthrin . Thus, urinary concentrations of 3-PBA may serve as a general biomarker of pyrethroid exposure, while cisDCCA represents a more specific biomarker for human exposure to CM. Currently, there are no published studies specifically assessing the occupational exposure to CM. One pyrethroid study investigated occupational exposure in Chinese cotton workers spraying deltamethrin, fenvalerate and a deltamethrin methamidophos mixture . Hardt and Angerer evaluated occupational exposure in individual workers after applying a mixture of up to 7 synthetic pyrethroids, including CM. Another study described occupational exposure to permethrin and fenvalerate , and a number of other studies have documented general pyrethroid exposure in non-occupational settings utilizing 3-PBA as a general biomarker of pyrethroid exposure . The primary objective of the present study was to investigate occupational exposure to CM by quantitating the daily urinary levels of cis-DCCA and 3-PBA before, during, and after the application of CM in a cohort of Egyptian agriculture workers who were spraying CM on cotton fields daily for up to 10 consecutive days. A bio-monitoring study on a subset of this Egyptian agriculture worker population determined that 94–96% of the dose was due to dermal exposure . While chlorpyrifos exposure has previously been characterized in these individuals , this is the first study to describe a longitudinal assessment of exposure to CM.A detailed description of the study setting was previously published , and a previous chlorpyrifos biomonitoring study on a subset of this Egyptian agriculture worker population estimated that 94–96% of the dose was due to dermal exposure . Briefly, the present study was conducted in Menoufia, one of 29 governorates in Egypt, which is located in the Nile River Delta north of Cairo. Daily urine samples were collected from a cohort of 37 Ministry of Agriculture workers which were divided into three job categories: applicators who spray the insecticide on the cotton crop with a backpack mistblower sprayer; technicians who walk the fields with the applicator in order to point out particular areas which need attention; and engineers who direct the work mainly from the edge of the field. These workers were assigned to 3 regions where CM was sprayed daily in 3–5 h work shifts for up to 10 consecutive days in the summer of 2008. The workers provided daily spot urine samples before, during, and after the insecticide application cycle. The urine samples used for analysis were collected just prior to start of the work day, on 24 h intervals at approximately 3 pm. One technician was included in the demographic analysis, but did not provide any urine specimens during the pyrethroid application and was therefore excluded from the current study. Samples were placed on wet ice in a cooler and transported to Menoufia University , where they were stored at −20 ◦C until being shipped to the State University of New York at Buffalo on dry ice for analysis. Creatinine concentrations were measured using the Jaffe reaction ; urinary cis-DCCAand 3- PBA concentrations are expressed as micrograms or nanomoles per gram creatinine. All protocols and questionnaires were approved by Institutional Review Boards of Menoufia University and Oregon Health & Science University, the institute administering the parent grant that funded the field studies.This research is part of a larger study by Ithaka S+R and sponsored by the United States Agricultural Information Network. The project seeks to explore the research practices associated with agriculture studies through interviews with agricultural scholars across the United States. Throughout the research process, we were guided by the questions “How do agricultural scholars at UC Davis do their research?” and “What research support services do the researchers use and/or need more of in order to best carry out their work?” These questions are of particular importance to the University Library because agricultural research, teaching and outreach support the land grant mission of UC Davis. Cooperative Extension was formed in 1914 and is a partnership between the US Department of Agriculture and land grant institutions.