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This case-control study aimed to investigate whether the levels of Hsp70 (HSPA1A) and Hsp27 (HSPB1) in plasma and lymphocytes were associated with the risk of chronic obstructive pulmonary disease (COPD) among coal workers. A total of 76 COPD cases and 48 age-matched healthy controls from a group of coal workers were included. The case group consisted of 35 COPD patients whose condition was complicated with coal workers' pneumoconiosis (CWP) and 41 COPD patients without CWP. Heat shock proteins (Hsps) in plasma and lymphocytes were detected by ELISA and flow cytometry, respectively. Multiple logistic regression models were applied to estimate the association between Hsp levels and COPD risk. Our results showed that plasma Hsp70 and lymphocyte Hsp27 levels were significantly higher and plasma Hsp27 levels were significantly lower in COPD cases than in controls (p < 0.01). No significant differences in lymphocyte Hsp70 levels were found between COPD cases and the matched subjects. Higher plasma Hsp70 levels (odds ratio (OR) = 13.8, 95 % confidence interval (CI) = 5.7-33.5) and lower plasma Hsp27 levels (OR = 4.6, 95 % CI = 2.0-10.5) were significantly associated with an increased risk of COPD after adjusting for confounders. Higher lymphocyte Hsp27 levels were only associated with an increased risk of COPD with CWP (OR = 6.6, 95 % CI = 2.0-22.1) but not with an increased risk of COPD without CWP (OR = 3.0, 95 % CI = 0.9-8.9). Additionally, there were strong joint effects of different Hsps on COPD risk. These results showed that higher levels of plasma Hsp70 and lower levels of plasma Hsp27 might be associated with an increased risk of COPD among coal workers. They may have the potential to serve as monitoring markers for COPD in coal workers.

Coal workers' pneumoconiosis (CWP) is an occupational pulmonary disease that occurs by chronic inhalation of coal dust. Coal workers' pneumoconiosis is divided into two categories depending on the extent of the disease as simple pneumoconiosis (SP) and progressive massive fibrosis (PMF). Development of CWP is associated with the activation of the immune system. Neopterin is a predictive biochemical marker of cell-mediated immune activation and elevated levels of neopterin are detected in body fluids of patients with immune-related diseases. The present study was aimed to investigate whether increased serum, urine and bronchoalveolar lavage (BAL) fluid levels of neopterin is associated with the development and/or severity of CWP. Mean serum neopterin levels in SP and PMF patients (10.72 +/- 0.98 nmol/L; 14.08 +/- 3.86 nmol/L, respectively) were significantly higher than those of control group (5.30 +/- 0.47 nmol/L) (P < 0.05). Although urinary neopterin levels were also increased in SP and PMF patients (235.17 +/- 7.40 micromol/mol creatinine; 256.05 +/- 9.43 micromol/mol creatinine, respectively) as compared with the control group (140.00 +/- 5.43 micromol/mol creatinine) (P < 0.01), they were within the normal concentration range. No significant difference was observed between serum and urinary neopterin levels of SP and PMF patients. A correlation was observed between serum and urinary neopterin levels of all subjects (r = 0.525, P < 0.01). Bronchoalveolar lavage fluid neopterin levels were significantly higher in patients with SP and PMF (22.67 +/- 2.9 nmol/L; 41.67 +/- 8.68 nmol/L, respectively) compared with control subjects (6.264 +/- 1.74 nmol/L) (P < 0.05, P < 0.01, respectively). The levels of neopterin in BAL fluid were also significantly higher in patients with PMF than in those with SP (P < 0.05). These findings indicate that elevated serum and BAL levels of neopterin may be considered as a suitable biomarker for the assessment of CWP.

The ILO classification of small and large opacities is the basis for the compensation of patients with pneumoconiosis. In order to validate the radiological findings, we compared the ILO classification with the gradings of pneumoconiosis in the post mortem investigation (n = 126). An ILO classification of 1/0 used as the threshold value for accepting the diagnosis of a pneumoconiosis was 100% sensitive with a specificity of 2%. With a value of 2/3 the sensitivity decreased to 60% and specificity increased to 74%. The grading of large opacities in the radiograph correlated well with the post mortem findings (rs = 0.71; p < 0.001). For accepting the diagnosis pneumoconiosis from the radiograph alone a threshold value of 1/0 is not specific. The ROC-plot revealed that specificity reached acceptable levels with an ILO classification of at least 2/3.

Two kinds of coal mine dust, low rank with high quartz (bituminous) and high rank with low quartz (anthracite), were assayed for ability to induce alveolitis and to stimulate interleukin-1 release from normal alveolar macrophages in vitro. Dust-elicited bronchoalveolar leukocytes were also assessed for their effects on macrophage-depleted splenocyte mitogenesis and their ability to produce interleukin-1. Quartz and titanium dioxide were used for comparison as toxic and inert dusts, respectively. Both coal mine dusts caused substantial release of interleukin-1 from normal alveolar macrophages in vitro and the levels were higher than those caused by quartz. Bituminous coal mine dust provoked acute but rapidly subsiding macrophage/neutrophil alveolitis which was greater than that provoked by titanium dioxide; anthracite caused less alveolitis than titanium dioxide and quartz caused large scale, persistent alveolitis. Whole bronchoalveolar leukocytes, including polymorphonuclear neutrophils, elicited by exposure to dust, were less inhibitory to lymphocyte mitogenesis than normal alveolar macrophages and bituminous coal mine dust-induced neutrophils were augmentary to lymphocyte mitogenesis; macrophages from inflamed lungs were, on the whole, inhibitory to lymphocyte mitogenesis. Alveolar macrophages from bituminous coal mine dust- or titanium dioxide-exposed lungs showed increased ability to release interleukin-1 on stimulation in vitro. These findings suggest that bronchoalveolar leukocytes elicited by coal mine dust could modulate immunity by means of interleukin-1 release and enhancement of lymphocyte proliferation.

Antinuclear antibodies (ANA) were detected using a mouse kidney substrate in 69 of 238 (29 percent) underground Utah coal miners at a titer of 1:16. At titers of 1:4 and higher, 52 percent were positive. The majority had a speckled pattern and were not directed against any previously characterized antigens. Fifteen of 28 with high titer ANA had reduced complement. The ANA was more apt to be present in those with coal workers' pneumoconiosis (CWP), and as ANA titer increased, the percentage with CWP increased. The ANA increased with both age and coal mine dust exposure. It is hypothesized that ANA and CWP both result from long-term dust exposure, but that there is insufficient evidence to implicate ANA in the pathogenesis of CWP.

A comparative immunological and microbiological study of experimental coalworkers' pneumoconiosis (CWP) was made in rats and mice subjected to long-term exposures of coal-mine dust aerosols. Such aerosols were realistically prepared at a concentration equal to the maximal level of respirable dust permitted by Federal standards and animals were exposed for lengths of time equal to human work contact. Among the factors studied were the production of IgA and lung reactive antibody, lung microflora and changes in pulmonary clearance. Additional experiments were concerned with the effects of passively administered lung antibody on the pulmonary clearance. It was found that both species responded immunologically in a similar manner to humans with CWP in that IgA levels were significantly elevated and lung reactive antibodies were stimulated. Coal-mine dust inhalation had little effect on the pulmonary inactivation of inhaled bacteria, but the concomitant occurrence of passively administered lung reactive antibody seemed to enhance the inactivation.

This work formed part of a series of studies devised to investigate immunological markers which it was considered might reflect individual susceptibility to the development of coalworkers' pneumoconiosis and especially progressive massive fibrosis. Estimations of T and B lymphocytes and white blood cell counts (WBCC) were performed on blood samples from 324 coalworkers grouped according to radiographic category of pneumoconiosis, age, and smoking habits. A subgroup of 43 men was further screened for both humoral anti-lung antibodies (ALA) and direct lymphocyte-mediated cellular cytotoxicity (LMCC) towards human embryonic lung fibroblasts (HEL). In addition 673 serum samples obtained during a previous study of autoimmune factors in coalworkers were screened for humoral antibodies to HEL cells. The only correlation found between category of pneumoconiosis and alterations in WBCC, percentage or absolute numbers of lymphocytes, or the presence of anti-lung antibodies was a decrease in a subgroup of T lymphocytes with increasing severity of pneumoconiosis. The major factor influencing these parameters in this study was the smoking status of the man. Smokers showed increased WBCC and lymphocyte numbers and a higher frequency of ALA and LMCC when compared with nonsmokers.

Sera from 2421 coalminers, representing all the radiological categories of pneumoconiosis, and from 260 healthy blood donors, as controls, were examined for antinuclear factor and rheumatoid factor. Antinuclear factors were present in 21.5% of sera from the controls and in 23.1% from the coalminers' group. Rheumatoid factor was present in 5.3% of coalminers and as expected occurred particularly in the few men with progressive massive fibrosis who also had rheumatoid disease. The combined prevalence of both factors showed an increase with age at all disease levels and a significant association with pneumoconiosis category only in men older than 60 years. This study provides no evidence that autoantibodies are likely to be of value in detecting men predisposed to the development of massive fibrosis other than those with rheumatoid disease.

Serum from 109 coal workers with simple pneumoconiosis, 114 with progressive massive fibrosis, and 130 with normal chest radiographics as control subjects was examined for rheumatoid and antinuclear factors, and antibodies against both native human IgG and Mycobacterium tuberculosis. A significantly greater prevalence of autoantibodies was observed in subjects with pneumoconiosis than in control subjects; however, a rheumatoid factor prevalence of 16% with observed inthe control subjects. No serologic differences were observed between subjects with simple pneumoconiosis and those with progressive massive fibrosis.

Twenty-five histocompatibility antigens have been measured in 100 coal miners with pneumoconiosis attending a pneumoconiosis medical panel and the results compared with a panel of 200 normal volunteers not exposed to dust. Chest radiographs were read independently by three readers according to the ILO U/C classification. On a combined score, 40 men were thought to have simple pneumoconiosis and 60 men complicated pneumoconiosis. The number of antigens tested and associations between antigens caused difficulties in assessing the statistical significance of differences in prevalence of antigens between groups of men. Using stringent criteria for statistical significance, no significant differences were found in antigen prevalences between miners and controls, or miners with simple or complicated pneumoconiosis. When a less stringent statistical approach was applied, three antigens appeared to have abnormal prevalences in these 100 miners by comparison with the normal volunteers. More detailed examination of these antigen prevalences in relation to radiographic category of pneumoconiosis did not provide any supportive evidence that these slight associations were of statistical or clinical significance. Reports on histocompatibility antigens in miners with pneumoconiosis are reviewed briefly and the results compared. There is no good evidence that any of the histocompatibility antigens so far tested are associated with a clinically important altered risk of simple or complicated pneumoconiosis when dust is inhaled.

The occurrence and severity of pneumoconiosis were studied in 100 coal miners with rheumatoid arthritis (RA) and compared to findings in a geographically relevant survey of coal workers' pneumoconiosis. Contrary to European reports, miners with RA were not found to have an excessive frequency or severity of pneumoconiosis. In 55 of these men, serum immunoglobulin levels and rheumatoid factor were compared with data from matched RA patients with no history of silica exposure. The immunochemical results were unrelated to the stage of pneumoconiosis, nor did they differ from those in the control group.