[Long-term therapy with a retard theophylline preparation]. / Dauertherapie mit einem Theophyllin-Retardpräparat.

The present study was conducted to investigate the therapeutic effect of long-term treatment with a slow-release theophylline preparation on the pulmonary functions FEV1 and peak exspiratory flow (PEF). A total of 908 patients took part in this open multicenter study. Treatment with the slow-release theophylline resulted in an increase of FEV1 and PEF of about 20% in asthma and between 11% and 14% in COPD. Apart from theophylline itself, the galenic nature of the slow-release formulation also contributed to the therapeutic effect.

[Ambulatory follow-up of soot dust exposed workers]. / Ambulante Verlaufsbeobachtungen russstaubexponierter Arbeitnehmer.

Since 1974 in a follow-up study 54 still exposed and 29 formerly exposed workers of a carbon black producing factory (Oranienburg, FRG) were asked anamnestically and investigated clinically including lung function tests and E.C.G. Evaluating our results we did not hardly find out any important pathological findings. Considering different periods of exposition there was no fundamental yearly decrease of the ventilation values of still exposed and formerly exposed workers in comparison to the normal population. An additional pulmonary care is not to be required beside the demanded occupational medical check-up.

[Ambulatory care of interstitial lung diseases]. / Ambulante Betreuung interstitieller Lungenerkrankungen.

Clinical symptoms, radiological finding and functional results of patients with interstitial lung diseases were followed in a dispensary about 10 years. We compared the progress of 10 patients with pulmonary fibrosis histologically proved and of 19 patients without any previous evidence of fibrosis but suspicious of developing fibrosis at present. In both groups we found a rising proportion of patients suffering from dyspnoe on exertion and from increasing impairment. Functionally a significant decrease of the vital capacity was found especially in patients with fibrosis. The course of oxygen tension during physical exercise on a bicycle ergometer was well correlated to the dyspnoe on exertion. An airflow obstruction already existing at the start of the observation period was found to have an unfavourable influence on the progress of the interstitial lung disease. Eight patients being suspicious of a developing fibrosis were investigated clinically. On 5 patients a pulmonary fibrosis could be confirmed. A treatment using corticoids was started. To find a progression of a known interstitial lung disease in due time, it is necessary to check thoroughly these patients functionally and radiologically in a dispensary at regular intervals.

[Clinical symptoms and findings in the upper airway of soot-exposed workers]. / Klinische Symptome und Befunde der oberen Atemwege bei russexponierten Werktätigen.

Under conditions of the channel black technique of the carbon black producing factory in Oranienburg, DDR, some inhalative noxious agents are discussed, especially dust of carbon black in concentrations three times higher than permitted and the climate is causing aggravated conditions. 58 still exposed, 35 formerly exposed workers and 60 control persons of the same age and smoking habits were asked using a questionnaire and they were examined clinically to find out disturbances of health in the upper airways. Complaints concerning chronic rhinitis partly complicated by crusts and sanguineous nasal secretion more frequently had been stated by exposed workers compared to the control persons. The rhinoscopical findings of the exposed workers and control persons are emphasizing the case history details. By it, more severe chronical mucosal findings were diagnosed in 29 percent of the exposed, but only in 9 percent of the control persons. Obstructions of the nasal breathing are not to be related to the profession in spite of the significant differences of the anamnestical data and clinical findings. On the contrary the disorders of smell seem to be more important concerning the soot exposed workers. The roentgenological findings of the paranasal sinus and the cytological results of nasal secretion do'nt give further hints. The importance of an exposition of more than 10 years is apparent concerning the described morbid changes. Significant fewer complaints concerning the ENT were stated by the formerly exposed workers than the still exposed. Special examinations by an ENT physician should be performed on workers exposed to carbon black having already longer persistent complaints particularly concerning chronical mucosal findings and disorders of smell.

[Clinical symptoms and findings in the lower airways of soot-exposed workers]. / Klinische Symptome und Befunde der unteren Atemwege bei russexponierten Werktätigen.

Eighty three still exposed and 46 formerly exposed workers, exposed especially to dust of carbon black and extreme heat climate conditions up to 2 and 30 years, were asked using a standardized questionnaire concerning complaints of the lower airways. The workers were investigated clinically, by X-rays and functionally to find out disturbances of health in the lower airways. The sputum was investigated cytologically. Moreover, the certificates of death were checked. The results were compared to those of 144 control persons living in the same region. The still exposed and the formerly exposed workers were suffering from chronic bronchitis, from non-specific bronchial hyperreactivity and from obstructive ventilatory disturbances in dependence on the duration of exposition more frequently than the control persons. But the mean values of the one-second value of forced expiratory volume in per cent of the vital capacity of every group were not different. Severe disturbances of the lung function were stated in some cases mostly exposed more than 20 years. On 3 workers, exposed more than 20 years, roentgenological signs of a pneumoconiosis were diagnosed demonstrating the fibrogenic effect of carbon black. The cytological findings of sputum didn't show any new aspects. Compared to the other people no deviating frequencies of causes of death were found, especially not more cases with neoplasma. The mostly less frequencies of symptoms and findings of the formally exposed workers were estimated as a hint for regression of the disturbance. The expected dependence of the signs on smoking habits was not recognized. So the exposition described was emphasized as a professional noxious factor, particularly as compared to the control persons important differences were found and the influence of the duration of exposition on the symptoms and findings was significant. Workers exposed to soot suffering from chronic bronchitis, nonspecific hyperreactivity, and especially obstructive ventilatory disturbances should be held in pulmonary dispensary in time.

[Possibilities for optimizing therapy with theophylline preparations. III. Ventilatory effect and pharmacokinetics of "new" Pulmophyllin]. / Optimierungsmöglichkeiten bei der Therapie mit Theophyllinpräparaten. III. Ventilatorische Wirkung und Pharmakokinetik von Pulmophyllin "neu".

Investigations comparing the preparations Pulmophylline "new", Pulmophylline and Aminophylline show that Pulmophylline "new" has a position between the two other drugs concerning the ventilatory effect and the pharmacokinetics. The effect of this preparation starts in a slower rate and lasts longer than that of Pulmophylline, the effect decreases in a quicker manner than that of Aminophylline. Replacement of the Ethoxytheophylline by the more efficient Theophylline seems to be the first step for the optimization of this drug-preparation. The diminished rate of side effects of Ethoxytheophylline is connected with an unfavourable pharmacokinetics and a smaller effect, as it is shown by investigations of other authors and by our own results.

[Reproducibility of the results of bronchial reactivity tests]. / Zur Reproduzierbarkeit von Ergebnissen bronchialer Reaktivitätsprüfungen.

383 patients with a bronchial hyperreactivity were repeatedly investigated during an observation period of 3 up to 6 years. The inhalative provocation test with nebulized histamine solution was used. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured by spirometry. The reduction of FEV1 in per cent of the initial value marked the degree of the bronchial hyperreactivity. The normalization was depending on the degree of the initial bronchial hyperreactivity. In 148 patients (36.6%) the provocation test results were normalized, e.g. FEV1 decreased less than 15% of the initial value. Patients with a low degree of the bronchial hyperreactivity, that means a decrease of FEV1 between 15 and 30% of the initial value, demonstrated the normalization of the provocation test significantly more frequent than patients with a higher degree of bronchial hyperreactivity. There was a considerable difference in course of the bronchial hyperreactivity of smokers and non-smokers. The latter tended to a more frequent normalization. A further influence of the course was stated with the age of patients. The younger ones had a higher tendency to normalization. Patients suffering from asthma bronchiale were mostly in the group with a higher degree of bronchial hyperreactivity and showed a rather stable course of it.

[Application of theophylline as an inhalant (author's transl)]. / Zur inhalativen Anwendung von Theophyllin.

The local tolerance and the functional efficacy of theophylline inhalant were investigated in 51 patients suffering from NSLD with reversible bronchospasm. In different doses aethophylline and aminophylline were nebulized using a jet or an ultrasonic nebulizer. FEV1 was controlled in fixed intervals and the patients were questioned about their subjective statements. At the end, a test with novodrin (isoprenaline)-spray was performed demonstrating the actual reversibility of the bronchospasm. In conclusion of our findings we can state: 1. Theophylline aerosols produced by a jet have neither an important subjective nor a functional efficacy. A prolongation of the inhalation time and the nebulized dose, respectively, has no better effects. 2. Aerosols of a 5% solution of theophylline produced by an ultrasonic nebulizer caused intensive local side-effects. Contrary to these aerosols those of a 2.5% solution were proved to be better tolerable and functionally effective, too, but only on patients with reversible bronchospasm. 3. Subjective statements and functional parameters were in a good accordance. 4. Serum levels of theophylline are not detectable with the method of SCHACK and WAXLER. The positive ventilatory effects after inhalation may suggest a topical action of the inhaled theophylline on the mucous membrane in the bronchial tree. 5. The increased values of FEV1 after the inhalation of theophylline are further increasing after the test with novodrin-spray. Therefore investigations of combination of theophylline and beta 2-sympathicomimetics in an aerosol seem usefully for optimization of the effect and for decreasing the side effects.

[The reproducibility of the bronchospasmolytic effects of isoprenaline tests repeated after long intervals under ambulatory conditions]. / Zur Reproduzierbarkeit von Bronchospasmolysetesten über lngere Zeiträume unter ambulanten Bedingungen.

The functional results of 3 bronchospasmolytic tests using 4 puffs of an isoprenaline-spray repeated in large intervals were compared on 104 patients suffering from obstructive lung diseases. The correlation coefficients and the coefficients of determination of the differences of the forced expiration volume in one second before and after the tests showed no good correspondence of the spasmolytic effects. It is to be stated that the dimensions of an improvement of the functional results can not be prognosticated, not even on condition that the functional situation before the test, the inhalant and the dose would be the same on the repeated test. Therefore an actual test using a known effective drug for the control has to be demanded for the investigation of on bronchospasmolytic inhalant.

[Efficacy of theophylline aerosols in obstructive lung diseases (author's transl)]. / Wirkung von Theophyllin-Aerosolen bei obstruktiven Erkrankungen der Atemwege.

We investigated aethophylline and aminophylline aerosols using a jet or an ultrasonic nebulizer in 51 patients suffering from NSLD with reversible bronchospasm. FEV1 was controlled in fixed intervals, and the patients were questioned about their subjective statements. A bronchospasmolytic test with isoprenaline spray at the end was performed to demonstrate the actual reversibility of the bronchospasm. Only theophylline aerosols produced by a ultrasonic nebulizer had a subjective and a functional efficacy. Theophylline aerosols of a 2.5% solution were proved to be better than aerosols of a 5% solution, but in comparison with the used sympathicomimetic drug isoprenaline spray, they were less effective. There was a good correlation with the subjective statements of the patients concerning the clinical effects. The concentration of the therapeutic aerosol seemed to be an important factor for the local tolerance and the ventilatory effects, measurable serum levels of theophylline could not be found. Therefore, the topical action of theophylline is considered to be responsible for the clinical effect.

[Clinical-experimental testing of drug aerosols (author's transl)]. / Zur klinisch-experimentellen Prüfung von Arzneimittelaerosolen.

After having demonstrated the used different clinico-experimental measures of the therapeutic efficacy of drug aerosols in the literature some proposals were placed referring to criterions selecting patients and to test conditions for groups of inhalants. A special selection of patients and the presence of a control group are emphasized. The correct valuation of the results is demanded.

[Clinical and cytological examinations on industrial workers exposed to mineraloilaerosols (author's transl)]. / Klinische und zytologische Untersuchungen bei Industriearbeitern mit Mineralölnebelexposition.

Clinical, roentgenological and spirometric examinations were performed on 217 industrial workers exposed to mineraloilaerosols and 197 control persons. No pathological results were to be found which could be connected with the professional employment. In both groups only in a few sputa lipid in respiratory epithelium cells was seen. We also did not find any evidence according to connection with the employment. The oilaerosolconcentrations were normaly, but during the unloading soot for a short time concentrations of anthrazeneoilaerosols up to 30 milligram per cubic meter were measured. Sputa provoced on persons with an empty stomach using aerosols of hypertonic salt solution were more effective than unprovoced sputa and sputa after meal.

[Generation and determination of pulmonary distribution disturbances (author's transl)]. / Erzeugung und Nachweis von pulmonalen Distributionsstörungen

Pulmonary distribution disturbances could be generated in patients with bronchial hyperreactivity by inhalation of a Falicain aerosol (Propoxipiperocainhydrochlorid); The inhomogeneities of ventilation and mechanics of breathing were determined by means of several simple and complex methods. Comparison between these methods of analysis of distribution shows that small alterations of inhomogeneity can be indicated also by simple screening tests. The results confirm the significant relationship between ventilation disturbance and pulmonary inhomogeneity. Distribution disturbance enhances both the obstructive and the restrictive component of a ventilation disturbance. These two components cannot be separated exactly by means of the parameters of ventilation and mechanics of breathing because of the influence of inhomogeneity. The generated disturbances of distribution and ventilation became regular after inhalation of an Alupent aerosol.

[Clinical and experimental examinations of drug-aerosols for the practice (author's transl)]. / Zur klinischen und experimentellen Prüfung von Arzneimittel-Aerosolen für die Praxis

Drug examination is regulated by drug legislation and special instructions for examination methods. Drug aerosols and inhalants for therapeutic purposes have to been examined regarding the different liquids, solutions, carriers and technical devices such as nozzles, ultrasonics and propellants for administration as a nebulized aerosol. Indications and contraindications of these inhalants, their local compatibility and reactions to the bronchial mucosa, their desired therapeutic effects, localized and general side-effects, localized and general side-effects have to be determined and are discussed. The data of these examinations have to be correlated with clinical and paraclinical results.

[Morphological changes in experimental lipid pneumonia (author's transl)]. / Das morphologische Bild der experimentellen Lipoidpneumonie

Male rats showed 6 and 8 weeks after aerosol application of mineral oil and interstitial pneumonia, histiocytic foreign body reaction with foam cells and a focal emphysema. Relations to the correspondent human disease are shortly discussed.

[Morphological changes in experimental lipid pneumonia (author's transl)]. / Morphologische Veränderungen bei experimenteller Lipoidpneumonie

The morphological changes were investigated by male rats after aerosol application of mineral oil above a period of three weeks. Beginning in the second week, there was a permanent increase of macrophages and foam cells in the alveolar septa and alveolar lumina in closed relation to the deposited mineral oil, visible by dark field illumination. The macrophages and foam cells showed a high activity of non-specific esterasis and acid phosphatasis whereas the activity of adenosine triphosphatasis clear decreased. In the third week the formation of focal granulomas started predominantly existing of histiocytes and only few foam cells.