[Ozone and bronchial asthma].
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Biomedical subjects
Publications and source records attributed to G Fruhmann.
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We performed diisocyanate inhalation tests (maximal concentration, 20 ppb; exposure time, 1-2 h) using toluene diisocyanate (TDI, n = 15) and diphenylmethane diisocyanate (MDI, n = 7) as well as methacholine challenges in 19 workers who had a clinical history of TDI/MDI-induced asthma. Additionally we tested volunteers who had no previous contact with diisocyanates: 10 healthy individuals with a negative methacholine test and 14 patients with asthma and a positive methacholine test were exposed to TDI. In all, 1 of the normal volunteers and 3 of the patients with asthma unrelated to diisocyanates showed a positive airway reaction to TDI, and 13 of the 19 diisocyanate workers displayed a positive result in the TDI/MDI inhalation test; however, only 6 of these 13 individuals reacted to methacholine. Furthermore, 3 of the 6 patients with a negative TDI/MDI challenge test demonstrated a significant response to methacholine. We conclude that bronchial hyperreactivity as evaluated by the methacholine challenge test is not closely related to isocyanate-induced bronchoconstriction and, therefore, the metacholine challenge is only of limited diagnostic value in patients with suspected isocyanate-induced asthma.
To evaluate pathophysiologic mechanisms of the predominantly nocturnal complaints in atopic bronchial asthma, the expression and function of beta 2-adrenoceptors on peripheral mononuclear leukocytes (pMNL), the cAMP--as well as the cortisol--plasma concentrations were studied in eight healthy men and ten so far untreated male asthmatic patients at 4-h intervals for 24 h. No difference was seen in the beta 2-adrenoceptor density (Bmax) on pMNL between healthy and asthmatic men (24-h means +/- SE: 908 +/- 59 sites per cell and 821 +/- 54 sites per cell, respectively). The equilibrium dissociation constant (Kd), however, was significantly higher in the asthmatic patients (24-h mean +/- SE: 8.8 +/- 1.2 pmol/L vs 3.0 +/- 0.2 pmol/L in healthy men, p less than 0.0001), which is equivalent to a lower affinity of the beta 2-adrenoceptors for the radioligand 125iodocyanopindolol. Bmax showed a statistically significant circadian variation, but Kd did not. The circadian variation in Bmax was reflected in the basal intracellular cyclic adenosine-monophosphate (cAMP) content of the cells investigated. High Kd values (equivalent to low receptor affinities) tended to be associated with small increases of the intracellular cAMP content after in vitro stimulation by 10(-7) mol/L isoprenaline (isoproterenol) (24-h mean +/- SE: 1.4 +/- 0.2 pmol/10(6) cells; r = -0.529, p = 0.05 at r = -0.549, n = 10). Plasma cAMP concentrations were found to be significantly lower in the asthmatic patients (24-h means +/- SE: 22.9 +/- 1.3 nmol/L vs 29.1 +/- 1.1 nmol/L, p less than 0.0001). Plasma cortisol concentrations were significantly higher in the asthmatic patients (24-h means +/- SE: 0.500 +/- 0.084 mumol/L vs 0.319 +/- 0.063 mumol/L). The results support the hypothesis that a lesion of the beta-adrenergic system contributes to the pathophysiology of atopic bronchial asthma. In the patients investigated in this study, such a lesion could be demonstrated in the affinity rather than in the number of beta 2-adrenoceptors expressed on peripheral cells of the immune system (pMNL). According to present-day knowledge of adrenergic effects on pMNL, such an affinity decrease of beta 2-adrenoceptors could account for overshooting immune responses. In association with other factors influencing respiratory function, it could be responsible for the predominantly nocturnal complaints in atopic bronchial asthma. Plasma cortisol concentrations did not appear to be related to the principal cause of "nocturnal asthma;" they rather reflected an endogenous defense mechanism to the disease.
Humidifier lung is a form of exogenous-allergic alveolitis caused by microbial growth in humidifiers and air conditioners. It was the aim of the present study to employ and test the ELISA method as an alternative to antibody determination. 134 employees in a large printhouse equipped with air conditioning plant were examined by us. Specific IgG antibodies against contaminated humidifier fluid were determined by means of a solid-phase radioimmunoassay (protein A RAST) that we had developed further. Alternatively we examined a commercially available ELISA method (Pharmacia IgG-RAST 40; enzyme: beta-galactosidase) and an assay based on protein A peroxidase. The influence of different test conditions was studied. All the methods examined proved suitable for determining the specific IgG antibodies. The commercial beta-galactosidase assay could be adapted to application on microtitre plates in a slightly modified form. In the peroxidase assay it is recommended to use very low serum and enzyme concentrations on account of its high sensitivity. Examination of all the 134 serum samples yielded a high correlation between the results of these two non-radioactive methods and those obtained with the protein-A RAST.
The university teacher in industrial medicine is guided by an autonomous self-responsibility to public interests protected by the fundamental law of the German Federal Republic. For the medical student about 8 hours practical work and an examination in the second clinical professional examination is prescribed. The teaching of the mutual relationships between industrial work and health is divided into: prevention and clinical aspects of industrial diseases, industrial hygiene, toxicology, industrial physiology (ergonomics), industrial psychology, rehabilitation and knowledge of giving expert opinion. The following are discussed as examples of research related to practice: the constant revision of the list of maximal concentration of work places, studies on the synergism of inhaled poisons, research into the causes of chronic bronchitis, pneumoconioses due to organic dusts and the discovery of aggresive antigens in work places previously considered safe.
68.8% of the workers of a metal factory have at least one pathological finding out of 11 parameters checked. The number of sick people increases from 57.1% in sedentary workers, to 64.5% in workers doing light or medium physical work, and 77.2% in heavy physical workers. The strongest trend, postulating a positive correlation between work and disease, can be found with the objective signs "chronic bronchitis", "inguinal hernia", and "pathological urine". Contrary to this positive trend in most medical findings, only hypertension and electrocardiographic changes are less frequent in heavy physical workers. The results obtained suggest, on the whole, an interrelationship between sickness and heavy physical work.
Seven out of eleven workers occupationally exposed to airborne papain developed immediate hypersensitive reactions, predominantly asthma and rhinitis. Skin tests and RAST with papain were positive in all symptomatic workers, but not in the four asymptomatic workers. Furthermore, out of forty non-exposed asthmatics, thirty-eight had negative RAST results and all had negative skin test results. Bronchial provocation tests with 0.15-0.5 mg papain performed in five patients with a positive case history showed in each case an immediate asthmatic reaction; in addition to that, one patient developed signs of a dual asthmatic reaction. Our results suggest that airborne papain is a highly immunogenic agent in humans, which induces type I allergic reactions in a large percentage of the exposed subjects.
A 58-year-old pharmaceutical worker regularly developed asthma and rhinitis when handling bromelain, a purified protease of pineapple (Ananas comosus), at her work-place, where she had been employed for about 10 years. RAST and prick test showed strong positive reactions to bromelain. Both inhalation test with 0.03 mg bromelain and peroral challenge by ingestion of 190 g pineapple resulted in asthmatic reactions; the latter challenge was accompanied by gastrointestinal symptoms. Five of six workers sensitized to papain, showed positive RAST and skin test results to bromelain, two of them also showed immediate asthmatic reactions after bronchial challenge with bromelain. Out of sixty asthmatics not exposed to airborne proteases but probably to these as constituents of foods, two had positive skin test results and eight had positive RAST results to bromelain; but in no case was there clear evidence for clinical sensitization. The presented data prove conclusively that bromelain is capable of inducing IgE mediated respiratory and gastrointestinal allergic reactions. Furthermore, there is evidence for immunological cross-reaction between the two plant proteases bromelain and papain in human subjects.
Two workers developed dermatitis, rhinitis, bronchitis, and asthma after occupational exposure to dusts of persulfate salts. The causative role of the persulfate salts could be confirmed by case history, skin tests, occupational exposure tests and by removal of the 2 workers from their jobs. Patch tests produced late cutaneous reactions. Occupational exposure at the working place for 8 h resulted in each case in a pathological increase of airway resistance. Withdrawal from occupational exposure to persulfate salts resulted in recovery within a few days. Our results suggest that chemically irritative or toxic effects of persulfate salts play the predominant role in the pathogenesis of the reported cases.
3 asthmatic patients, occupationally exposed to vapors of toluylene diisocyanate (TDI), responded with a moderate to strong elevation of airway resistance up to the 26th h after inhalation challenge by 0.006--0.02 ppm TDI. No changes in chest radiographs and in DLCO were found. In none of the patients' sera, isocyanate-specific antibodies could be detected by RAST and Ouchterlony test. Change of job resulted in one case in an immediate interruption of the asthmatic symptoms, whereas in 2 patients recovery was slow over a period of 3 to 8 months and not complete. Our investigations suggest a toxic effect of isocyanates, which depends on their concentrations, and an important pharmacological reaction; but, up to now, there were no signs of allergic mechanisms.
The development or exacerbation of an asthmatic condition is more often than is commonly realized attributable to the inhalation during work of substances which have either antigenic properties or induce physico-chemical damage to the mucous membranes. The following substances were found to play a causal role in the development of asthma in exposed persons: penicillin dust, dust inhaled during the threshing of grain, persulfate, formalin, inorganic cooling agents. Procedures to ascertain the aetiology of these occupation-induced obstructive bronchial disease are reviewed. The inhalation challenge test, exposure tests at the place of work and removal of the affected person from contact with the suspected antigen are discussed in respect of their diagnostic value.
87 patients with bronchial asthma underwent skin test, RAST and measurment of airway resistance before and after inhalation of control solution as well as at least 10 times after each of one to four bronchial provocations (making up a total of 171 tests) with extracts of house dust, house dust mite, animal dander, mould spores and pollen in increasing concentrations. An actual clinical significance of the skin test reactions was found in 60% of all cases and of the RAST results in 66% of all cases. The overall agreement between skin test results and RAST results was 61%. The correlations between the different tests depended on the degree of hypersensitivity, on the tested allergen and on whether the results of skin test and RAST, respectively, were positive or negative. There existed a good correlation between the results of all three test methods and case history only for pollen allergens and animal dander. Noticeably often negative RAST results with house dust and mould spores, as well as positive skin tests with house dust mite and mould spores could not be confirmed by the provocation test. Important indications for a bronchial provocation test in asthmatics are doubtful case history, doubtful skin test or RAST results with the problem-allergens house dust, house dust mite and mould spores; the bronchial provocation test is especially commendable when drastic or cumbersome therapeutic measures (immunotherapy, change of home, change of job) are to follow or if late asthmatic reactions are expected.
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