Agricultural dust exposure and pneumoconiosis The prevalence of histologic-determined cigarette smoking in this population was 54.5%, which is significantly higher than population-based data on smoking prevalence among Hispanic males (Perez-Stable 2001). However, smokers have excess injury deaths (RR = 1.86), which are heavily weighted in coroner’s cases (Leistikow et al. 2000; Wen 2005). Furthermore, young Hispanics living in the United States have higher rates of smoking than non-Hispanic youth (Perez-Stable 2001). There also may be some degree of misclassi- fication 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 emis- sions 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 agricul- tural 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 (Table 4) is of unknown significance. Cigarette smoking was associ- ated with increased odds for other respiratory health outcomes, as expected. Examination of Figure 3 shows that farm work and smok- ing have additive effects on the milder grades of small airway fibrosis. However the data also indicate that there is a maximal response (threshold effect) to these agents that might account for the negative interaction in the multivariate analyses. Morbidity and mortality studies in sev- eral countries have observed an association of COPD and agricultural work (Brackbill et al. 1994; Lamprecht et al. 2007; Schenker 1998), but this is not observed in all agricul- tural populations (Blair et al. 2005). This asso- ciation is observed concomitant with a lower mortality rate from lung cancer, reflecting the lower known smoking prevalence among agri- cultural workers (Singleton and Beaumont 1989). We observed a strong association of mineral dust exposure with interstitial fibrosis and pneumoconiosis, after adjustment for cig- arette smoking. However, we also found inde- pendent associations of mineral dust exposure and emphysema, chronic bronchitis, lymph node fibrosis, and mineral dust small airways disease. Our findings suggest one possible mechanism for a causal association of agricul- tural 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 (Nieuwenhuijsen et al. 1998, 1999). 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 par- ticles, 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 ambi- ent inhalable particle concentrations (par- ticulate matter ≤ 10 µm; PM10) in the United States, often exceeding the National Ambient Air Quality Standard of 150 µg/m3 averaged over 24 hr (U.S. Environmental Protection Agency 2006). Chow et al. (1992, 1993) describe in detail the physicochemical characteristics and sea- sonal variability of PM in Fresno. During the winter months, the highest PM10 (particu- late matter with aerodynamic diameter < 10 µm) concentrations have a dominant PM2.5 fraction (i.e., fraction of particles < 2.5 µm in aerodynamic diameter). These particles consist mostly of carbonaceous constituents (espe- cially particles < 0.3 µm) as well as ammonium nitrate and sulfate (0.3–2.5 µm). 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 domi- nated by fugitive dusts, mostly associated with coarse (i.e., 2.5–10 µm) 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 nonurban sites (Alexis et al. 1999). During this time, the PM10 daily (arithmetic) aver- age concentration in Fresno was 43.5 µg/m3, and the maximum 24-hr PM10 concentra- tion 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 (NOx) 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 lev- els averaged 0.0054 ppm with a maximal con- centration of 0.017 ppm (Alexis et al. 1999). In a previous study involving a subset of this population, we used a systematic approach to determine the distribution of ambient parti- cles in the human lung and their potential role in tissue remodeling (Pinkerton et al. 2000). 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 reten- tion with subtle but quantifiable changes in tissue remodeling were clearly established. The importance of this site as a target for particle- induced injury is well established in occupa- tional settings (Green 1983). The centriacinar region is the primary site of injury in coal worker’s pneumoconiosis (Kleinerman et al. 1979), asbestosis-induced injury (Craighead et al. 1982), and silica- and silicate-induced injury (Craighead et al. 1988). Case reports of silicate pneumoconiosis have been reported in farmworkers from the central valley of California (Sherwin et al. 1979). Cigarette smoking (Niewoehner et al. 1974) and highly polluted urban centers (Churg et al. 2003) also induce injury in this region, and there is considerable evidence that respiratory bronchiolitis precedes the Table 7. Age-adjusted mineral content of the lung by agricultural work and cigarette smoking status (mean ± SE). Mineral component Mg quartz/100 g lungb SEM/XRS analyses: Particles analyzed per case Total mineral particles per gram dry lung No. of silica particles per gram dry lung Median circular equivalent diameter silica (μm) No. of AlSi particles per gram dry lung Median circular equivalent diameter (AlSi) (μm) Difference in size between silica and AlSi particles No. 35 37 37 37 36 37 35 36 [1] Nonagricultural nonsmoker 5.13 ± 3.82 1505.4 ± 178 20.83 ± 16.30 16.83 ± 6.92 0.52 ± 0.05 4.00 ± 12.86 0.68 ± 0.08 0.16 ± 0.07 [2] Nonagricultural smoker 18.87 ± 4.08 1,238 ± 167 38.83 ± 16.30 31.78 ± 6.93 0.48 ± 0.05 7.05 ± 12.86 0.50 ± 0.10 0.02 ± 0.08 [3] Agricultural worker [4] Agricultural worker nonsmoker smoker 12.31 ± 3.42 1,051 ± 149 33.94 ± 15.37 25.18 ± 6.53 0.51 ± 0.05 8.76 ± 12.12 0.80 ± 0.08 0.29 ± 0.07 18.02 ± 3.42 1,457 ± 178 101.79 ± 13.31 45.33 ± 5.65 0.50 ± 0.04 56.46 ± 10.50 0.57 ± 0.07 0.07 ± 0.06 Two outliers were removed from these analyses, both nonagricultural workers. One of these had widespread granulomatous lung disease, the other had worked as a stonemason. Codes 1–4 for different categories are represented in the final column as significant differences. aDifferences between adjusted means p < 0.05. bThis association became nonsignificant when age was added into the model. All other associations remained significant. cXRD. Environmental Health Perspectives • volume 117 | number 6 | June 2009 Significant differencesa 1:2, 1:4c None 4:1, 4:2, 4:3 4:1, 4:3 None 4:1, 4:2, 4:3 3:2, 3:4 3:2, 3:4 993