The fate of particles is not well established, and there is little information on the distribution and retention of particles under conditions of ambient exposure. One purpose of this study was to design and implement an approach that would allow the assessment of particle retention as well as histologic analysis of response in different lung compartments. Our findings in this regard have been previously published and show that the deposition of particles is primarily in the centriacinar portion of the lung lobule . Unfortunately, no reported epidemiologic studies have directly assessed environmental exposure to mineral dusts and interstitial lung and airway disease in farmers or farm workers, although respiratory symptoms have been associated with exposure to agricultural dusts with high mineral content . A few studies, however, have suggested that pneumoconiosis and restrictive lung disease are increased in some agricultural populations exposed to mineral dusts. A fundamental question remains whether occupational exposure to agricultural dusts can cause pulmonary fibrosis, persistent inflammation,aeroponic tower garden system and cell/tissue remodeling in specific regions of the lungs where these mineral dusts are present.
The objective of this study was to document and quantify pathologic lesions in lung tissues from consecutive Hispanic males autopsied by the coroner’s office in Fresno, California, and to determine their relationship to agricultural work and to mineral dust retained in the lungs. We focused on pneumoconiosis and lesions of the small airways.We thank S. Smiley-Jewell for assisting with manuThis research has been funded in part by National Institute for Occupational Safety and Health U07/ CCU906162, U.S. Environmental Protection Agency grants R826246 and RD832414, and the Alberta Lung Association. The authors declare they have no competing financial interests. Received 2 September 2008; accepted 25 February 2009.2000. We report that young male agricultural workers have a higher prevalence of pneumoconiosis and small airway disease associated with mineral dust exposure than do non-agricultural workers living in the same environment.Left lungs from 112 Hispanic male autopsies were collected at the Fresno County coroner’s office from June 1994 to June 1995. Demographic information including age, residence duration in Fresno County, and occupational histories were obtained from the medical examiner and the coroner’s files. Smoking histories were available for a minority of subjects; therefore, smoking status was classified by pathologic criteria. The study subjects ranged in age from 16 to 73 years and had died suddenly or unexpectedly. An autopsy was performed at the coroner’s office to determine the cause and manner of death, as dictated by state statute. The autopsies were performed within 12‒24 hr after death. The research team independently evaluated a sagittal slice of lung.
The project was thoroughly reviewed and approved by the Human Subjects Review Committee of the University of California, Davis. We did not have access to nor did we contact the next of kin.The left lung of each deceased individual was cannulated through the left main stem bronchus and inflation fixed with 2% glutaraldehyde at a hydrostatic pressure of 30 cm of water for 2 hr from a constant-pressure gravity apparatus. The lungs were cut in the sagittal plane to include the main stem bronchus, hilar structures, and the medial aspect of both the upper and lower lobes of the left lung. If the left lung was not suitable because of trauma, the right lung was processed in an equivalent manner. Initial fixation and cutting was done by the coroner’s staff. The lung section was stored in fixative and shipped to the University of California, Davis. On arrival, each lung was photographed from the cut sagittal surface as well as a medial view, and selected gross features were documented on a standard form; these included pleural pigmentation, fibrosis, and emphysema. Selected airways were micro-dissected and examined for mucous plugs or aspirated material within the lumen.Gross examination revealed varying amounts of black pigmentation in the pleura, around bronchovascular bundles, in the centriacinar zones of the parenchyma, and within hilar lymph nodes. Airway micro-dissection showed that dust accumulation was less proximally but became distinct around small airways. Grossly recognizable emphysema was rarely seen. Many lungs showed parenchymal hemorrhage consistent with a traumatic death. Smoking-related small airway disease and mineral dust‒associated small airways disease were seen in 54.5% and 28.6% of all cases, respectively . Pneumoconiosis was observed in 20.9% of subjects, lymph node fibrosis associated with mineral dust accumulation in 48.7%, pathologic changes consistent with chronic bronchitis in 56.3%, and microscopic emphysema in 23.6%.
Asthmalike inflammation and airway wall remodeling were seen in 26.8% of 112 subjects . The crude prevalence of mineral dust small airways disease, pneumoconiosis, and pathologic changes consistent with chronic bronchitis was significantly higher among farm workers than among non-agricultural workers and approached statistical significance for lymph node fibrosis and emphysema. In univariate models of the relationship between pathologic disease and mineral dust deposition as evaluated by polarized light microscopy on tissue sections, mineral dust deposition was strongly and significantly associated with interstitial fibrosis, mineral dust small airway disease, pneumoconiosis, pathologic changes consistent with chronic bronchitis, emphysema, and lymph node fibrosis . These associations remained significant after adjustment for age and smoking status. Cigarette smoking was associated with an OR of < 1 for mineral dust small airways disease, but this association was small compared with the very strong association with mineral dust exposure . Agricultural work was kept in the model for chronic bronchitis over mineral dust because it had a higher point estimate , although it did not achieve statistical significance at p < 0.05. Fibrosis of the walls of membranous and respiratory bronchioles was seen in most of the subjects. Examples of airway lesions in the groups are shown in Figure 2. The fibrosis was significantly greater in the upper lobes compared with the lower lobes. Forty-one percent of the nonsmoking, non-agricultural workers showed no fibrosis of their respiratory bronchioles . Very few non-agricultural workers exhibited a severe grade of airway fibrosis . Agricultural workers had more severe grades of fibrosis. The severity of the small airway disease increased in the following order: nonsmoking non-agricultural workers; nonsmoking agricultural workers; smoking non-agricultural workers; smoking agricultural workers. The effects of smoking and agricultural work on grade of small airway disease appeared additive . By bright field and polarized light microscopy,dutch buckets for sale opaque and birefringent dust in farmers’ respiratory bronchioles was highly correlated with small airways fibrosis . There was a highly significant relationship between agricultural work and a finding of pneumoconiosis : A total of 32.1% of agricultural workers had either macules or nodules in their lungs compared with only 8.3% of non-agricultural workers . This association persisted in a multivariate analysis controlling for age and cigarette smoking. Prevalence of pneumoconiosis increased to 41.5% and 18.6% in agricultural and non-agricultural workers, respectively, when interstitial fibrosis was included as a feature of pneumoconiosis . Pneumoconiosis was also significantly associated with an increased score for birefringent mineral particles in the walls of small airways . The correlation between pneumoconiosis 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 .
CSi and AlSi were the most prevalent exogenous minerals found in the lungs for all groups . Milligrams of quartz per 100 grams of lung, measured by XRD analysis, were significantly increased in agricultural workers who smoked compared with nonsmoking non-agricultural workers and in non-agricultural smokers compared with non-agricultural nonsmokers . Logistic regression analysis, adjusted for age and smoking, showed a significant relationship between the amount of quartz determined gravimetrically in the lung and the presence of mineral dust small airway disease . SEM/XRS analysis showed greater numbers of total mineral particles, silica particles, and AlSi workers compared with non-agricultural workers and in smokers compared with nonsmokers . 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 significantly larger than silica particles overall, with the greatest difference seen in the nonsmoking agricultural workers . Mineral dust small airway disease was significantly 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.The lungs of deceased farm workers living in an agricultural region of California had significantly higher rates of pneumoconiosis and interstitial fibrosis than the lungs of deceased non-agricultural workers living in the same general environment. Furthermore, the farm workers showed higher prevalence of chronic obstructive pulmonary disease , including emphysema, pathologic changes consistent with chronic bronchitis, and small airways disease than the lungs of deceased non-agricultural workers living in 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 birefringent particles in the small airways, the amount 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 pneumoconiosis was confirmed by three separate approaches. First, and most important, by light microscopy we directly confirmed a relationship 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 significantly associated with small airway fibrosis. Third, we showed by SEM and XRS that the total number of mineral particles was greater in the lungs of agricultural workers than in non-agricultural workers and that their concentration was significantly associated with airway fibrosis. We thus demonstrate 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 farm workers. Our data also indicate that mineral dusts contribute to both obstructive and restrictive lung disease processes. The findings reported here are remarkable in view of the young age of the study population. Mineral dust pneumoconioses are generally considered to have long latencies until clinically apparent, on the order of 10‒20 years . The latency period until early pathologic changes that are not radiologically or clinically evident is unknown. The cases examined in this study were young Hispanic males who had lived an average of 16 years in Fresno County. Approximately one-half of these subjects were farm workers, whereas the others were in other blue-collar occupations. None of these individuals 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 airway and interstitial lung disease associated with agricultural work. Case–control studies have suggested an association of idiopathic pulmonary fibrosis with agricultural dust exposure, and specifically with animal dust/vegetable dust, but these studies have involved multiple associations without verification of exposure . 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 control lymph nodes . A study using SEM and energy-dispersive X-ray analysis suggested that silica/silicate exposure might be a risk factor for IPF .Similar to our findings, Nasr et al. 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 “idiopathic” may be an inaccurate description for some cases of IPF.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 . However, smokers have excess injury deaths , which are heavily weighted in coroner’s cases . Furthermore, young Hispanics living in the United States have higher rates of smoking than non-Hispanic youth .