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Pulmonary disease caused by the inhalation of a biological agent
BRITISH THORACIC
AND
TUBERCULOSIS
ASSOCIATION
119
Only men with records of long periods of employment showed an excess mortality from respiratory diseases. Where possible postmortem reports and histological material were obtained from the Pneumoconiosis Panels and hospitals where the patients had died and were reviewed by Dr. J. C. Wagner. Carcinoma of bronchus had not been seriously under-recorded on the death certificates. A mesothelial tumour had only been recorded as a cause of death on five death certificates but after review of the available histological material a further five pleural and 11 peritoneal mesotheliomas were identified; seven of the latter had been registered as deaths due to cancer of the gastrointestinal tract. A STUDY OF SOMEIMMUNOLOGICALFACTORSASSOCIATEDWITH ASBESTOSIS W. RAYMOND PARKES(London)
This preliminary study (done in collaboration with Dr. M. Turner-Warwick) of tissue antibodies -antinulear factors (ANF) and rheumatoid factors (RF)-was undertaken for two reasons:(1) The clinical syndrome of asbestosis is similar to that of the ‘mural’ type of cryptogenic fibrosing alveolitis (or diffuse interstitial fibrosis) in which an increased prevalence of these antibodies has been found. (2) RF is present in some cases of coal pneumoconiosis with or without arthritis. Chest radiographs were correlated with ANF and RF (DAT and latex fixation) in 77 unselected persons with a history of past asbestos exposure who were referred to the Pneumoconiosis Medical Panel in London. Radiographic appearances were graded quite simply as ‘round’ or ‘linear and irregular’, and according to size and coarseness and their extent in the conventional lung zones. The presence or absence of ‘honeycombing’ was noted and so was pleural thickening in lung zones. Only unequivocal changes were recorded and referred to as ‘obvious changes’. ANF and RF were found singly or together in 39 of the 77 cases-about 50 per cent ‘obvious lung changes’ occurred in 57 cases, pleural changes alone in 8 cases, and ‘normal’ radiographs in 12 cases. ANF and RF were present in 29 cases with ‘obvious changes’. Only weak positive latex tests were present in four cases. Antibodies were absent in 24 cases. That is, antibodies were present in 55 per cent of the cases. By contrast, ANF and RF are each found in approximately five per cent of the general population. There appeared to be a trend suggesting that coarse opacities are more likely to be associated with antibodies than fine opacities. All four subjects who had unusual, small, round shadows had antibody. ‘Honeycombing’ was not apparently associated more or less with the presence of antibodies. Of 19 subjects followed for five years six of 10 with progressive disease had antibodies, whereas antibodies were detected in the form of a doubtful positive latex reaction in only one out of nine with non-progressive disease. The possible significance of these findings was discussed. It was suggested that asbestos-provoked lung fibrosis tends to select out the five per cent of the general population with enhanced tissue antibody production though the antibodies themselves may not play any part in pathogenesis.
PUI
It was thought that certain cases of respiratory illness among workers in a factory using a dry powder containing proteolytic enzyme derived from Bacillus subtilis were due to inhalation of the
material. The incidence and clinical features were not consistent with disease due to infection. nor with primary irritant proteolytic effects being the sole cause. Supporting evidence for allergy was obtained from skin and inhalation tests, showing that the enzyme component of the material could give rise to responses characteristic of those due to immediate (type 1) reagin-mediated reactions and also of late (type III) precipitin-mediated ones. Symptoms had included breathlessness, with or without wheezing or chest tightness, cough which was usually unproductive but sometimes associated with scanty mucoid sputum, chest pain. and malaise. Twenty out of twenty-five of those with breathlessness as the predominant symptom showed evidence of sensitization to enzyme extracts when skin-prick-tested. Evidence of sensitization was not confined to atopic individuals and the material is believed to be capable of causing reaginic and non-reaginic asthma and allergic alveolitis. The pattern of illness in a given patient is likely to vary with such factors as the physical state of the material handled and the intensity and frequency of exposure to it; also his immunological state, both as to whether or not he is atopic as well as to whether he has become sensitized to the material. Irrespective of any harm that may be caused by proteolytic effects, severe or repeated attacks of illness due to type III allergic reactions can lead to irreversible impairment of pulmonary function, which may sometimes develop insidiously. so the emphasis must be on prevention.
INHALATION TESTSIN PATIENTSWITH RESPIKATORY ALLERGYTO B. SuBTILIsENZYMES PROFESSOR J. PEPYS(London)
Inhalation tests were employed for the investigation of three workers who had become allergic to enzyme products of B. subtifis. They had no past history of atopic disorders or of extrinsic sensitivity to the common allergens and no reactions were given to these on skin testing. All three patients presented with evidence of obstructive ventilatory defect, which was poorly reversible either with adrenergic drugs or corticosteroids. One had a slight restrictive ventilatory defect as well. They were all highly sensitive to the enzyme preparations as shown by their histories of sometimes severe asthma following exposure and by strong immediate reactions to prick tests with the purified enzymes and with extracts of the commercial preparations. Intracutaneous tests were made in two of them and one gave a dual, that is an immediate followed by a late, reaction. The inhalation tests provoked immediate asthmatic reactions which resolved, to be followed by a second more prolonged and severe reaction four hours or so after the test. In two of the patients there was a leucocytosis but no eosinophilia after the test. In the third, who gave only late asthmatic reactions to the first two tests, subsequent tests caused both immediate and late reactions, and the leucocytosis was accompanied by an increasing peripheral blood eosinophilia. The persistent airways obstruction with which they presented is similar to that seen in non-atopic ‘bird-fanciers’ with extrinsic non-atopic asthma, which is thought to be mediated by precipitating antibody and which also develops some hours after inhalation tests. Precipitation reactions were given against the enzyme preparations by the affected workers but the significance of this is not yet clear, as similar reactions were obtained with the sera of non-exposed subjects.
NOTICE OF MEETINGS The next meeting of the Association will be in conjunction with the West Country Chest Society at Exeter University on Friday and Saturday, April 9th and 10th (Particulars of this meeting were given in a previous issue of ‘Tubercle’ and will be circulated to members in detail). The Joint Meeting of the B.T.T.A. and the Thoracic Society will be at Lancaster University,
AND
TUBERCULOSIS
ASSOCIATION
119
Only men with records of long periods of employment showed an excess mortality from respiratory diseases. Where possible postmortem reports and histological material were obtained from the Pneumoconiosis Panels and hospitals where the patients had died and were reviewed by Dr. J. C. Wagner. Carcinoma of bronchus had not been seriously under-recorded on the death certificates. A mesothelial tumour had only been recorded as a cause of death on five death certificates but after review of the available histological material a further five pleural and 11 peritoneal mesotheliomas were identified; seven of the latter had been registered as deaths due to cancer of the gastrointestinal tract. A STUDY OF SOMEIMMUNOLOGICALFACTORSASSOCIATEDWITH ASBESTOSIS W. RAYMOND PARKES(London)
This preliminary study (done in collaboration with Dr. M. Turner-Warwick) of tissue antibodies -antinulear factors (ANF) and rheumatoid factors (RF)-was undertaken for two reasons:(1) The clinical syndrome of asbestosis is similar to that of the ‘mural’ type of cryptogenic fibrosing alveolitis (or diffuse interstitial fibrosis) in which an increased prevalence of these antibodies has been found. (2) RF is present in some cases of coal pneumoconiosis with or without arthritis. Chest radiographs were correlated with ANF and RF (DAT and latex fixation) in 77 unselected persons with a history of past asbestos exposure who were referred to the Pneumoconiosis Medical Panel in London. Radiographic appearances were graded quite simply as ‘round’ or ‘linear and irregular’, and according to size and coarseness and their extent in the conventional lung zones. The presence or absence of ‘honeycombing’ was noted and so was pleural thickening in lung zones. Only unequivocal changes were recorded and referred to as ‘obvious changes’. ANF and RF were found singly or together in 39 of the 77 cases-about 50 per cent ‘obvious lung changes’ occurred in 57 cases, pleural changes alone in 8 cases, and ‘normal’ radiographs in 12 cases. ANF and RF were present in 29 cases with ‘obvious changes’. Only weak positive latex tests were present in four cases. Antibodies were absent in 24 cases. That is, antibodies were present in 55 per cent of the cases. By contrast, ANF and RF are each found in approximately five per cent of the general population. There appeared to be a trend suggesting that coarse opacities are more likely to be associated with antibodies than fine opacities. All four subjects who had unusual, small, round shadows had antibody. ‘Honeycombing’ was not apparently associated more or less with the presence of antibodies. Of 19 subjects followed for five years six of 10 with progressive disease had antibodies, whereas antibodies were detected in the form of a doubtful positive latex reaction in only one out of nine with non-progressive disease. The possible significance of these findings was discussed. It was suggested that asbestos-provoked lung fibrosis tends to select out the five per cent of the general population with enhanced tissue antibody production though the antibodies themselves may not play any part in pathogenesis.
PUI
It was thought that certain cases of respiratory illness among workers in a factory using a dry powder containing proteolytic enzyme derived from Bacillus subtilis were due to inhalation of the
material. The incidence and clinical features were not consistent with disease due to infection. nor with primary irritant proteolytic effects being the sole cause. Supporting evidence for allergy was obtained from skin and inhalation tests, showing that the enzyme component of the material could give rise to responses characteristic of those due to immediate (type 1) reagin-mediated reactions and also of late (type III) precipitin-mediated ones. Symptoms had included breathlessness, with or without wheezing or chest tightness, cough which was usually unproductive but sometimes associated with scanty mucoid sputum, chest pain. and malaise. Twenty out of twenty-five of those with breathlessness as the predominant symptom showed evidence of sensitization to enzyme extracts when skin-prick-tested. Evidence of sensitization was not confined to atopic individuals and the material is believed to be capable of causing reaginic and non-reaginic asthma and allergic alveolitis. The pattern of illness in a given patient is likely to vary with such factors as the physical state of the material handled and the intensity and frequency of exposure to it; also his immunological state, both as to whether or not he is atopic as well as to whether he has become sensitized to the material. Irrespective of any harm that may be caused by proteolytic effects, severe or repeated attacks of illness due to type III allergic reactions can lead to irreversible impairment of pulmonary function, which may sometimes develop insidiously. so the emphasis must be on prevention.
INHALATION TESTSIN PATIENTSWITH RESPIKATORY ALLERGYTO B. SuBTILIsENZYMES PROFESSOR J. PEPYS(London)
Inhalation tests were employed for the investigation of three workers who had become allergic to enzyme products of B. subtifis. They had no past history of atopic disorders or of extrinsic sensitivity to the common allergens and no reactions were given to these on skin testing. All three patients presented with evidence of obstructive ventilatory defect, which was poorly reversible either with adrenergic drugs or corticosteroids. One had a slight restrictive ventilatory defect as well. They were all highly sensitive to the enzyme preparations as shown by their histories of sometimes severe asthma following exposure and by strong immediate reactions to prick tests with the purified enzymes and with extracts of the commercial preparations. Intracutaneous tests were made in two of them and one gave a dual, that is an immediate followed by a late, reaction. The inhalation tests provoked immediate asthmatic reactions which resolved, to be followed by a second more prolonged and severe reaction four hours or so after the test. In two of the patients there was a leucocytosis but no eosinophilia after the test. In the third, who gave only late asthmatic reactions to the first two tests, subsequent tests caused both immediate and late reactions, and the leucocytosis was accompanied by an increasing peripheral blood eosinophilia. The persistent airways obstruction with which they presented is similar to that seen in non-atopic ‘bird-fanciers’ with extrinsic non-atopic asthma, which is thought to be mediated by precipitating antibody and which also develops some hours after inhalation tests. Precipitation reactions were given against the enzyme preparations by the affected workers but the significance of this is not yet clear, as similar reactions were obtained with the sera of non-exposed subjects.
NOTICE OF MEETINGS The next meeting of the Association will be in conjunction with the West Country Chest Society at Exeter University on Friday and Saturday, April 9th and 10th (Particulars of this meeting were given in a previous issue of ‘Tubercle’ and will be circulated to members in detail). The Joint Meeting of the B.T.T.A. and the Thoracic Society will be at Lancaster University,