Biomedical subjects
Publications and source records attributed to J Pepys.
Histamine has been measured in whole blood and in the plasma of twenty-three subjects following exercise testing of seventeen asthmatics and six normal controls. Whole blood histamine rose in both asthmatics and controls and was associated with a concomitant rise in the basophil count. Plasma histamine in the peripheral venous blood only rose in one patient who developed urticaria after exercise.
Occupationally related asthma developing in three patients due specifically to exposure to 1,5-naphthylene di-isocyanate (NDI), a hot curing agent used in manufacturing rubber, has been confirmed for the first time using bronchial provocation testing. This substance has been thought to be safer than toluene di-isocyanate (TDI) and diphenylmethane di-isocyanate (MDI) because of its relatively high melting point (120 degrees C). Each patient worked in the same factory and the circumstances of exposure were similar. Provocation testing was also performed with TDI in concentrations up to 0.018 parts per million (ppm) and MDI in concentrations up to 0.02 ppm, to which the patients had been exposed in the past, but no reactions were elicited. None of the patients had increased bronchial reactivity judged by histamine lability and exercise testing. Each patient was advised to give up his job, but two of the three could not find alternative employment and remained exposed. Three-year follow-up shows that airways narrowing has persisted in those who have remained exposed.
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A double-blind placebo controlled study of sodium cromoglycate, beclomethasone dipropionate and salbutamol by inhalation was designed to test their effect on respiratory symptoms and changes in ventilatory capacity in cotton mill workers. All three drugs showed some beneficial effect. Salbutamol was the most effective drug studied, in all groups of workers. Beclomethasone dipropionate was also significantly effective particularly in workers with byssinosis or exertional dyspnoea. Sodium cromoglycate was the least effective of the three. Possible mechanisms of action of these drugs are described.
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Twenty-one patients are described who developed asthma, or evidence of a peripheral airways reaction, while working in the electronics industry and exposed to solder flux fumes containing colophony (pine resin). This selected group contained five patients with pre-existing asthma. Fourteen patients had never smoked. Prick-testing with common environmental antigens gave one or more positive reactions in nine patients. The diagnosis was confirmed by occupational-type provocation tests in all workers with colophony-based cored solder, and reproduced by exposure to the fumes of heated colophony alone. Control subjects did not react to the test with colophony. The clinical findings and provocation test reactins have features of a hypersensitivity reaction, although so far specific antibodies have not been found.
Out of twenty patients with a history of asthma or urticaria attributed to food substances, ten reacted on oral challenge: seven with asthma, one with asthma and urticaria and two with urticaria alone. In five of the eight asthmatic reactors, the symptoms developed within a few sec and there was no associated rise in free venous plasma histamine. In those remaining, two with asthma, two with urticaria and one with both, the symptoms developed only after 20-30 min. A rise in free plasma histamine occurred only in the two subjects with urticaria alone. The third with urticaria and asthma did not have blood estimations performed. Sodium cromoglycate in a dosage of 800 mg a day for 1 week, or a single dose of 1.0 g by mouth, did not block any of the reactions. By inhalation it blocked the asthmatic reactions which developed within a few sec of challenge.
A teacher with breathlessness of insidious onset developed acute symptoms on return home following his discharge from hospital. His flat was found to have extensive dry rot (Merulius lacrymans). Precipitins and specific IgE and IgG antibody against M. lacrymans were present and intracutaneous testing gave a typical dual skin reaction. Pulmonary physiology demonstrated airflow obstruction with a low DLCO and KCO, and a chest X-ray showed diffuse micronodular shadowing, maximal in the mid-zones. Inhalation challenge testing provoked a combined asthmatic reaction without a change in DLCO. Rapid clinical recovery and more gradual radiographic and physiological improvement followed cessation of exposure to the antigen.
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Five atopic laboratory workers with asthma and other manifestations of allergy to rats and mice were sensitive to low-molecular-weight urine proteins--an alpha2-globulin in the rat and a prealbumin in the mouse. Positive skin prick and inhalation test reactions to the urine proteins were obtained; and radioallergosorbent tests (R.A.S.T.) for specific IgE antibody were also positive. These findings show that proper control of the collection and disposal of the animals' urine is necessary to minimise the likelihood of sensitisation.
Symptoms and signs typical of extrinsic allergic alveolitis occurred in 24 workers in a stationery factory. The illness was caused by inhalation of a water aerosol contaminated by microorganisms, and although no specific organism has been incriminated, affected workers had serum precipitins to the contaminated water, and the illness could be reproduced by inhalation challenge tests.
1. Tests against rabbit antiserum to Candida albicans showed about 40 protein antigens in cytoplasmic extract compared with two in a commercial test extract, which contained mainly polysaccharide (mannan) antigens. 2. Positive precipitin tests to the mannan preparation were recorded in 40% of 56 asthmatics on systemic corticosteroids and 37% of 56 rhinitis patients not so treated. The titres were slightly higher in the corticosteroid group. There was no increase in precipitins over 0-9 months in asthmatics treated with beclomethasone dipropionate aerosol (BDA) by inhalation, or over 0-12 months in rhinitis patients treated with BDA nasal spray. No positive reactions to the purified protein fraction were recorded. 3. Radioallergosorbent tests for specific IgE antibody showed a higher incidence of positive results with whole C. albicans yeast cells than with purified cytoplasmic protein. There was a higher incidence of positive results to protein in patients on systemic corticosteroids than in the other patients. No change in incidence occurred in asthmatics on BDA. The number of positive results in 56 rhinitis patients increased on BDA from 28 to 37 for yeast cells, and from 7 to 16 for cytoplasmic protein. This was attributed to C. albicans challenge tests. 4. Specific IgA antibodies to yeast cells were detected in 48/56 asthmatics on systemic corticosteroids, and there were no significant changes over 0-9 months on BDA. The corresponding figures for rhinitis patients were 25/56, and again there were no significant changes over 0-12 months on BDA.
Six workers with a diagnosis of occupational asthma and one with chronic bronchitis were examined for sensitivity to epoxy resin systems and certain of their components. In six cases the chemical agent responsible for their symptoms was identified by careful inhalation challenge testing, simulating their exposure at work and thus providing a precise aetiological diagnosis. In one worker asthma followed exposure to triethylene tetramine fume; four were sensitive to acid anhydrides, three to phthalic acid anhydride as a fume or powder and one to trimellitic anhydride. On worker thought to be sensitive to toluene di-isocyanate gave negative reactions to this and positive reactions to a phthalic acid anhydride epoxy resin and another thought to have asthma from acid anhydride fumes was found to be sensitive only to toluene di-isocyanate. Immediate, non-immediate or combined asthmatic reactions were elicited.
A method is presented for measuring the uptake of Aspergillus fumigatus protein by IgG antibodies from human serum. The human IgG is first isolated with an anti-IgG conjugated immunosorbent and then incubated with radio-iodinated A. fumigatus protein. A group of twenty-three control sera gave the same background levels as tests without sera. The highest uptake of A. fumigatus protein was given by the sera of patients with aspergilloma, and lower values were obtained with six out of thirteen sera from patient's with asthma and twenty-five out of twenty-eight sera from patients with asthma and pulmonary eosinophilia, i.e. allergic bronchopulmonary aspergillosis. These results were in agreement with precipitin tests, Inhibition studies with unrelated antigens showed that the reactions were specific for the A. fumigatus protein, of which more was bound by test sera than with a crude extract.