Schenker et al. all groups (Table 7). Milligrams of quartz per 100 grams of lung, measured by XRD analy- sis, were significantly (p < 0.05) increased in agricultural workers who smoked compared with nonsmoking nonagricultural workers and in nonagricultural smokers compared with nonagricultural nonsmokers (Table 7). Logistic regression analysis, adjusted for age and smoking, showed a significant relation- ship between the amount of quartz deter- mined gravimetrically in the lung and the presence of mineral dust small airway dis- ease (OR = 1.114; 95% CI, 1.007‒1.233) (p < 0.05). SEM/XRS analysis showed greater numbers of total mineral particles, silica parti- cles, and AlSi workers compared with nonag- ricultural workers and in smokers compared with nonsmokers (Table 7). The sizes of the mineral dust particles by type of particle and subject group are also shown in Table 7. The average median circular equivalent diameters for silica and silicate particles were < 1 µm for all four groups. Silicate particles were sig- nificantly (p < 0.05) larger than silica particles overall, with the greatest difference seen in the nonsmoking agricultural workers (Table 7). Mineral dust small airway disease was signifi- cantly (p < 0.05) associated with the number of silica, AlSi, and total mineral dust particles in the lung in univariate models and with total particle number in multivariate models. Discussion The lungs of deceased farmworkers living in an agricultural region of California had significantly higher rates of pneumoconio- sis and interstitial fibrosis than the lungs of deceased nonagricultural workers living in the same general environment. Furthermore, the farmworkers showed higher prevalence of chronic obstructive pulmonary disease (COPD), including emphysema, pathologic changes consistent with chronic bronchitis, and small airways disease than the lungs of deceased nonagricultural workers living in 16 14 12 y 10 c n ue 8 q e rF 6 4 2 0 992 the same general environment. Multivariate analyses showed that these pathologic lesions were strongly associated with mineral dust in the lungs, as assessed by grade of birefrin- gent particles in the small airways, the amount (milligrams per gram) of quartz, and number of silica and silicate mineral dust particles in digested lung samples. The study indicates that agricultural work in the central valley of California carries a significant risk for mineral dust small airway disease, pneumoconiosis, and COPD. The relationship between mineral dust exposure, small airway disease, and pneu- moconiosis was confirmed by three separate approaches. First, and most important, by light microscopy we directly confirmed a relation- ship between airway fibrosis, pneumoconiosis, and birefringent mineral particles. Second, in a subgroup of the cases, we showed, in bulk samples of lung tissue, that CSi was signifi- cantly associated with small airway fibrosis. Third, we showed by SEM and XRS that the total number of mineral particles (silica and silicates) was greater in the lungs of agricul- tural workers than in nonagricultural workers and that their concentration was significantly associated with airway fibrosis. We thus dem- onstrate that mineral dusts play an important role in lung disease for agricultural workers and that mineral dusts need to take their place beside the well-established roles of organic dusts and smoking in causing lung disease in farmworkers. Our data also indicate that min- eral dusts contribute to both obstructive and restrictive lung disease processes. The findings reported here are remark- able in view of the young age of the study population. Mineral dust pneumoconioses are generally considered to have long laten- cies until clinically apparent, on the order of 10‒20 years (Smith and Leggat 2006). The latency period until early pathologic changes that are not radiologically or clinically evi- dent is unknown. The cases examined in this 0 0–0.7 0.7–1.4 > 1.4 Non-Ag, nonsmoker Ag, nonsmoker Non-Ag, smoker Ag, smoker Farmworker and smoking status Figure 3. Fibrosis score (by quartiles) of agricultural work and smoking status for first-generation respira- tory bronchioles. Abbreviations: Ag, agricultural; Non-Ag, nonagricultural. Increasing scores for fibrosis were associated with both agricultural work and smoking status. The effects of cigarette smoke and farm dust exposure appear additive. study were young Hispanic males who had lived an average of 16 years in Fresno County. Approximately one-half of these subjects were farmworkers, whereas the others were in other blue-collar occupations. None of these indi- viduals died of respiratory disease, and most were in apparent good health before death. This is the first population-based sample that we are aware of that shows small air- way and interstitial lung disease associated with agricultural work. Case–control studies have suggested an association of idiopathic pulmonary fibrosis (IPF) with agricultural dust exposure, and specifically with animal dust/vegetable dust, but these studies have involved multiple associations without verifi- cation of exposure (Baumgartner et al. 2000). A case–control study of inorganic particles in the pulmonary hilar lymph nodes of patients with IPF found an association of increased silicon and aluminum compared with con- trol lymph nodes (Kitamura et al. 2007). A study using SEM and energy-dispersive X-ray analysis suggested that silica/silicate exposure might be a risk factor for IPF (Monso et al. 1990). IPF is also strongly associated with cigarette smoking in epidemiologic studies (Taskar and Coultas 2006). Similar to our findings, Nasr et al. (2006) have recently shown that cigarette smokers with interstitial fibrosis have increased burdens of silica and silicates in their lungs. Taken together, these studies indicate that exposure to inorganic dusts, whether overt or occult, may be a more common cause of pulmonary fibrosis than currently recognized and that the term “idio- pathic” may be an inaccurate description for some cases of IPF. Table 5. Associations of pneumoconiosisa with agricultural work, smoking, and mineral dust par- ticles in small airways: univariate analysis. Exposure Agricultural work (%) No agricultural work Chi-square, p-value Never smoked (%) Ever smoked Chi-square, p-value Mineral dust particles (%) Score < 0.25 0.25–0.9 0.9–2.03 (max) Chi-square, p-value Pneumoconiosis 32.1 8.33 8.16 31.2 χ2 = 8.62, p = 0.0033 χ2 = 8.68, p = 0.0032 0 8.62 66.7 χ2 = 46.1, p = < 0.0001 aDefined as presence of macules and/or nodules. Table 6. Independent association of pneumoco- niosis with agricultural work: multivariate logistic regression. Dependent variable Covariate OR (95% CI) Pneumoconiosis Age 1.001 (0.962–1.042) Smoking 6.208 (1.612–23.91) Agricultural work 5.362 (1.547–18.58) ovlume 117 | number 6 | June 2009 • Environmental Health Perspectives