[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 association of maximal expiratory flow-volume curve and the response of nonspecific bronchial responsiveness was studied in 265 normal and asthmatic subjects. Bronchial hyperresponsiveness to acetylcholine was found in 143 subjects. These hyperreactive persons had already significantly reduced maximal expiratory flow rate at 75%, 50% and 25% vital capacity before the test started. Besides, we found a significant correlation between the provocative dose and the flow-volume parameters, although resistance was in the normal range. We concluded that the flow rates at middle and low lung volumes may be an important determinant of bronchial sensitivity to acetylcholine.
Three years after starting to work as a hairdresser a 33-year-old woman developed urticaria on contact with hairbleach. After a further four years rhinoconjunctivitis set in and later also bronchial asthma on contact with such bleaches. Extensive tests revealed hypersensitivity to widely used persulphate-containing bleaching liquids which ultimately forced the patient to give up her profession. The causative role of this group of chemicals was proven by positive skin tests and specific workplace-related provocation tests. But specific IgE antibodies could not be demonstrated. The findings suggest a pseudoallergic reaction.
Pulmonary involvement in tuberous sclerosis (pTS) is very rare and seems to be associated with a more benign course, compared to tuberous sclerosis without pulmonary manifestation (TS). Furthermore, pTS seems to be related to lymphangiomyomatosis (LAM). We present the case of a 33-year-old woman in whom the overlap of TS, pTS and LAM is demonstrated. Treatment with medroxyprogesterone was initiated, but without success.
Beta 2-adrenoceptor agonists act against bronchoconstriction by stimulating beta 2-adrenoceptors in bronchial smooth muscle. However, tachyphylaxis has been argued to occur because of beta 2-adrenoceptor down-regulation following therapy with beta 2-adrenergic agents. To investigate receptor alterations, human peripheral mononuclear leukocytes are frequently used, since human lung tissue is not easily available. In order to study whether beta 2-adrenoceptors in MNL reliably reflect the conditions in the human lung tissue, we compared MNL and human lung tissue of 18 patients who had to undergo lung resection. Ten patients were untreated, and eight had bronchodilator therapy prior to therapy with terbutaline because of bronchoconstriction. Both in human lung and MNL, the beta 2-adrenoceptor subpopulation was characterized by competition experiments with the beta 1-selective antagonist CGP 207.12 A and the beta 2-selective antagonist ICI 118.551. In MNL, a significant decrease in the density of beta 2-adrenoceptors was found in treated but not in untreated patients, while the antagonist affinity of the beta 2-adrenoceptors remained unchanged. However, in lung parenchyma, which was obtained at the very same time from the same patients, no down-regulation of the total amount of beta 2-adrenoceptors could be measured. It is concluded that MNLs are a reliable model for studying properties of beta 2-adrenoceptor regulation. However, the hereby obtained results show that MNLs do not reflect the conditions of beta 2-adrenoceptors in human lung tissue. Human lung tissue is found to be less susceptible than human MNL for beta 2-adrenoceptor down-regulation by terbutaline treatment at therapeutic doses.(ABSTRACT TRUNCATED AT 250 WORDS)
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We investigated 10 healthy control subjects, 15 asthmatics without occupational exposure to isocyanate, and 45 "isocyanate workers" with workplace-related respiratory symptoms. In none of the cases did the skin test or the IgE-RAST reveal a type I sensitisation to isocyanate. The investigation programme included a lung function test, provocation with metacholine or acetylcholine, and an isocyanate challenge test under controlled clinical conditions. A total of 17 "isocyanate workers", and 1 asthma patient with no occupational exposure to isocyanate revealed a positive bronchial obstructive reaction to the isocyanate challenge test. In 10 of the patients, the MCH (ACH) test was positive; 2 were chronically obstructive, but 6 patients showed no signs of bronchial hyperreactivity. No significant differences in the severity of the bronchial obstructive reaction induced by isocyanate exposure were observed between patients with and those without bronchial hyperreactivity. In the group of "isocyanate workers", the isocyanate challenge test was observed to be superior to the MCH (ACH) provocation test in terms of sensitivity (0.68 versus 0.62) and specificity (1.0 versus 0.61), this difference being more obvious in the overall group (sensitivity 0.71 versus 0.62; specificity 0.98 versus 0.49).
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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.