Factors relating to the individual susceptibility of coalminers to the development of progressive massive fibrceis. Final report on CEC Contract 7246-14/8/001

1. Considerable evidence has accumulated over the years to illustrate that inhalation of minerals such as silica, beryllium and asbestos can affect both humoral and cellular immunity. Few investigations of a similar kind have been undertaken in workers exposed to coal dust. The following series of studies was designed to provide someinsight into the effects that coal dust inhalation has on various aspects of the immune system. In addition, the basis forindividual variability of reactions to the dust retained was sought by investigation of certain genetic markers.2. Susceptibility to chronic pulmonary disease has been associated with a genetically-based deficiency of alpha-1-antitrypsin. The inhalation of coal dust may compound such a deficiency and cause excessive loss of lung function. Groups of men whose lung functions were better, worse or the same as predicted from their age, heightand dust exposure were examined for differences of serum levels or phenotypes of alpha-1-antitrypsin. It was assumed that most of the men with chronic obstructive pulmonary disease, probably emphysema,would have worse than expected lung function. “”There were no cases with the Pi ZZ phenotype. normally associated with severe deficiency.The distribution””of men with Pi MZ, MS or SS was similar throughoutthe lung function groups. . Within the whole group studied,men with the worse than expected lung function had the highest levels of alpha-1-antitrypsin regardless of smoking habit, although smoking was shown to stimulate serum levels. Thus reduced levels of alpha-1-antitrypsin were not related to excessive loss of lung function in this study and it was concluded that factors other than those examined must be important in determining susceptibility to pulmonary disease.3. Serum samples from coalminers, representing all radiological categories of pneumoconiosis, and from a group of controls were screened for antibodies to Escherichia coli. Low levels ofthese antibodies may indicate a reduction in immune competence.There was no relationship between the percentage of.men with reduced titres of Escherichia coli antibody and the presence ofpneumoconiosis.4. Certain immunoglobulin levels may be increased in a variety of pulmonary disorders. Serum levels of IgG, IgA and IgM were measured in a group of coalminers representing all the radiological categories of pneumoconiosis and in a group ofcontrols. Increases in IgG and IgA correlated positively with the radiological category of pneumoconiosis and even men withno radiological signs of pneumoconiosis had elevated levels when compared with non dust-exposed controls. Smoking habit caused some variation in mean levels in the control group but the increased values in the coalminers were not related to differences in the distribution of the cases by smoking habit within the pneumoconiosis categories.5. The total white blood cell count and the percentage and absolute numbers of T and B lymphocytes were estimated in blood samples from a group of coalminers who represented all the radiologicalcategories of pneumoconiosis. No association between the radiological category of pneumoconiosis and the above parameters could be found. The smoking status of the man was the major factor influencing the absolute numbers of lymphocytes and thetotal white blood cell count.6. Serum samples from coalminers representing all the radiological categories of pneumoconiosis were screened for anti-lung cell antibodies. The low levels of antibody which were found in a few sera did not correlate with the radiological category of pneumoconiosis though a weak association with smoking was noted.The ability of lymphocyte samples to kill cultured lung cells was assessed in coalminers representing all the categories of pneumoconiosis. No correlation of cytotoxic activity with pneumoconiosis category was found. The majority of the cytotoxic samples came from smokers or ex-smokers. There was little evidence that the inhalation of coal dust induced the development of systemic immunity to lung tissue.There have been reports of associations between increased susceptibility to some diseases and the occurrence of certain histocompatibility antigens. Several groups of coalminers with progressive massive fibrosis and controls with similar dust exposures but without radiological signs of pneumoconiosis were typed for a wide range of antigens. The coalminers studied came from South Wales and the Midlands and North East areas of England. There were no significant differences between coalminers with progressive massive fibrosis and the controls with respect to the distributions of the antigens detected. However, trends in some of the results appeared to be consistent with other reports suggesting an association between the presence of B12, or its rare subtype Bw45t and pulmonary fibrosis.8. In summary, this study has found no evidence that the inhalation of coal dust, unlike other particulates such as silica and asbestos, evokes a systemic response to lung tissue as measured by the methods used nor does it upset the proportions of T and B lymphocyte subsets in circulation, while the changes in serum immuno globulins levels detected are common to many pulmonary disorders. Low levels of the anti-protease enzyme alpha-1-antitrypsin do not seem to influence the extent of lung damage following dust exposure. Our limited study of relationships between genetic markers and susceptibility to lung fibrosis has not been conclusive.Nevertheless, there is still substantial evidence to support the involvement of immune phenomena in the pathogenesis of pulmonary fibrosis. Any injury to the collagen and elastin framework of the lung whether caused directly or indirectly by dust inhalation may stimulate the immune system. These immune reactions are likely to occur locally within the lungsince there is no evidence that the typical patient with fibrotic lung disease has pathological processes elsewhere. A better understanding of the processes involved may be gained by examination of bronchoalveolar fluids and cells from dust-exposed animals and patients with fibrotic lung disease. “”