severity of the small airway disease (respiratory bronchioles and membranous bronchioles) increased in the following order: nonsmoking nonagricultural workers; nonsmoking agri- cultural workers; smoking nonagricultural workers; smoking agricultural workers. The effects of smoking and agricultural work on grade of small airway disease appeared addi- tive (Figure 3). By bright field and polarized light microscopy, opaque and birefringent dust in farmers’ respiratory bronchioles was highly correlated with small airways fibrosis (r = 0.66). There was a highly significant relation- ship between agricultural work and a find- ing of pneumoconiosis (Table 5): A total of 32.1% of agricultural workers had either mac- ules or nodules in their lungs compared with only 8.3% of nonagricultural workers (p = 0.003). This association persisted in a multi- variate analysis controlling for age and ciga- rette smoking. Prevalence of pneumoconiosis increased to 41.5% and 18.6% in agricultural and nonagricultural workers, respectively, when interstitial fibrosis was included as a feature of pneumoconiosis (p < 0.0001). Pneumoconiosis was also significantly associ- ated with an increased score for birefringent mineral particles in the walls of small airways (Table 5). The correlation between pneumo- coniosis and the mineral dust score was r = 0.57. In multivariate models that controlled for age and cigarette smoking, agricultural work was a significant independent predictor of pneumoconiosis (OR = 5.362; 95% CI, 1.547–18.58) (Table 6). CSi and AlSi were the most prevalent exogenous minerals found in the lungs for 5.19 (1.6 to 16.82) 2.29 (1.03 to 5.10) 2.36 (0.91 to 6.13) 2.06 (0.93 to 4.54) Disease category Interstitial fibrosis Pneumoconiosis Chronic bronchitisc Emphysema Lymph node fibrosis Mineral dust small airways disease 3.23 (1.31 to 7.99) Agricultural dust exposure and pneumoconiosis Figure 2. Composite photomicrographs of representative examples of first-generation respiratory bronchioles. All images were taken at the same magnification; bar = 200 µm. (A) Proximal respiratory bronchiole from a 43-year-old nonsmoking, nonagricultural worker. There is no evidence of fibrosis or inflammation. The airway has divided into three separate segments, each attended by a small pulmonary artery. Grade 0 for all features. (B) Proximal respiratory bronchiole from an 18-year-old nonagricultural worker who smoked. The respiratory bronchiole and its bifurcations shows thickening of the wall by fibrosis, muscular hypertrophy, chronic inflammation, and numerous smoker’s macrophages within the lumen of the airway and adjacent alveoli. This airway was considered grade 2 for fibrosis. (C) Proximal respiratory bronchiole from a 56-year-old nonsmoking agricultural worker. The airway wall shows marked thickening, mild inflammation, and no smoker’s macrophages in the alveoli. This bronchiole was considered grade 3 for fibrosis. (D) Proximal respiratory bronchiole from a 23-year-old agricultural worker who smoked. The airway wall shows marked thickening, moderate to severe inflammation, and numerous smoker’s macrophages in the lumen of the airway and adjacent alveoli. This bronchiole was considered grade 3 for fibrosis. 12.35 (3.39 to 44.90) 161.8 (21.4 to > 999) 166.8 (17.56 to > 999) 4.68 (1.75 to 12.52) 16.08 (4.35 to 59.46) 9.15 (3.11 to 26.9) Mineral dust Age Smoking status Mineral dust Age Smoking status Mineral dust Age Smoking status Agricultural workerd Age Smoking status Mineral dust Age Smoking status Mineral dust Age Smoking status 6.21 (1.39 to 27.62) 1.05 (1.01 to 1.10) 5.03 (1.12 to 22.68) 575.4 (39.4 to > 999) 1.035 (0.99 to 1.08) 0.116 (0.022 to 0.618)b 453 (24.96 to > 999) 0.96 (0.914 to 1.013) 6.09 (0.88 to 41.904) 2.58 (0.87 to 7.72) 1.032 (0.99 to 1.08) 23.93 (8.00 to 71.54) 5.62 (1.04 to 30.24) 1.14 (1.07 to 1.25) 9.63 (1.66 to 55.94) 12.54 (3.04 to 51.7) 1.03 (0.99 to 1.07) 0.43 (0.15 to 1.20) Table 4. Associations between disease, agricultural work, and mineral dust in small airways: logistic regression [OR (95% CI)]. Univariate association OR (95% CI) Agricultural work Mineral dust deposition 1.90 (0.69 to 5.26) Multivariate association (Adjusted for age and smoking status)a Variable OR (95% CI) aMultivariate models always contained age and smoking status unless otherwise specified. They were checked for interactions between smoking status, grade of birefringent pig- ment in airway walls, and age. The model with both agricultural work and birefringent pigment was kept if both variables were significant or if one acted as a confounder to the other (changed the adjusted point estimate > 15%). Smoking status association was of similar size and significance whether the more inclusive variable ever smoked was used or current smoker, which excluded nine subjects. bSmoking protective against mineral dust small airway disease. cDefined by pathologic criteria. dAgricultural worker was kept in the model over mineral dust as the point estimate was larger and CI tighter, but both were inferior to smoking status for odds of chronic bronchitis. The univariate association with smoking status was 21.01 (7.94–55.57). Environmental Health Perspectives • volume 117 | number 6 | June 2009 991