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The aim of our prospective multicentric study was to develop a screening method for pulmonary hypertension in patients with chronic lung diseases. We investigated 710 patients in 10 hospitals: 315 males and 109 females with chronic obstructive pulmonary disease, and 286 males with silicosis. Manifest pulmonary hypertension was defined as pulmonary artery pressure greater than 20 mmHg (2.7 kPa) at rest. The multivariate statistical method used was a stepwise discriminant analysis. In males with chronic obstructive pulmonary disease, the diameter of the right descending pulmonary artery, forced expiratory volume in one second (FEV1) arterial oxygen tension (PaO2) at rest, and age turned out to be relevant for discrimination of groups with and without manifest pulmonary hypertension. For females the FEV1/FVC (forced vital capacity) ratio replaced the absolute value of FEV1 in the calculated discriminant function. In females, sensitivity and specificity were below 80%. In males, both were distinctly above 80%. In silicosis, the diameter of the right descending pulmonary artery was much less important, since it could frequently not be measured precisely. In these cases, precision of the prediction of about 80% could only be obtained by combined evaluation of spirometry, PaO2 during exercise, and body plethysmography. The calculated discriminant functions are appropriate for screening patients with risk of pulmonary hypertension. For different chronic lung diseases, and for both sexes, different combinations of parameters are relevant. The method is recommended to select patients who should undergo an invasive examination of pulmonary haemodynamics.

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One and a half years antinuclear autoantibodies (ANA) against Scl-70 and U1-RNP were found in the serum of a quartz dust exposed worker before the clinical manifestation of the progressive systemic sclerosis (PSS). Only a discrete lung fibrosis and an enlargement of the heart was seen at the time of the first autoantibody detection. Because workers with an intensive and long-lasting quartz dust exposition take a high risk to develop PSS a sensitive ANA-screening is indicated at minimum suspicion of chronic collagen disease. The detection of a high ANA-titer in a clinical healthy person may give a hint for the possible future development of such a disease and requires the observation of the clinical course and the paraclinical and immunological parameters. A lung fibrosis and/or an enlargement of the heart in X-ray photographs would indicate visceral early manifestations of the PSS before skin symptoms appear.

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There are closed relations between progressive systemic sclerosis (PSS) and exposure to quartz dust in the GDR. The recognition of PSS as an occupational disease is regulated by law. By analysis of the dust exposed working places a limit for silica concentrations were fixed. It is unlikely, that silica concentrations below 10% in the respirable dust induce a PSS. There are no significant differences in lung function of PSS-patients with and without quartz exposure.

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As to the examination of pulmonary haemodynamics the microheartcatheterization for sounding the right ventricle and the pulmonary artery should be found more acceptance in numerous pulmological and cardiological laboratories for verifying pulmonary hypertension, in preliminary examinations for vitium cordis, in intensive medical care for the continuous registration of haemodynamic parameters or to obtain expert opinion in connection with an occupational disease. Feasible measuring technique and method are put forward for making comparable evaluations. Reference values of haemodynamic parameters at rest and during bicycle exercise in sitting and lying position and regressions calculated on oxygen consumption and on age dependence are set forth. Critical suggestions on obtaining variables are given.

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For evaluation of reference values of airway resistance measured by forced oscillation technique (Ros) in connection with physical exercise, 193 healthy persons were examined. In this study could be shown that reference values measured at rest are also valid under exercise conditions to find out functional disorders.

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Calcium antagonists may provide an effective approach to the treatment of pulmonary hypertension disorders. Under this aspect we examined 44 patients by right heart catheterisation at rest and at exercise before and after sublingual application of a single dose of 20 mg nifedipine (Corinfar) as well as under continuous dosage of 30-60 mg daily. In patients with latent pulmonary hypertension we ascertained an efficient significant decrease of PAP, 15 of 18 patients were responders. This protective effect persists in the longterm studies after 1 year as well as after 2 years at equal magnitude. In patients with manifest pulmonary hypertension the influence on pulmonary hemodynamics was not so efficient. This behaviour is caused by morphological fixation of pulmonary hypertension. Therefore the determination of magnitude of pulmonary hypertension by right heart catheterisation is necessary for evaluation of nifedipine therapy.

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In healthy persons, without respiratory abnormalities, by physical exercise and hypoxia pulmonary hypertension can be induced. It could be shown that increasing physical exercise has a more pronounced influence upon the value of PAP, whereas increasing hypoxia has a more pronounced influence upon PO2-V.

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The following study was undertaken as a contribution to a therapeutic programme of pulmonary hypertension. The existence of a functional vascular component in patients suffering from silicosis complicated by chronic latent or manifest pulmonary hypertension has to be assumed. In these cases a therapeutic influence of aminophylline could be observed. The influence of repeated exercise was discerned by means of control group. Furthermore the importance of a rapid analysis of drug serum concentration during investigation by means of high pressure liquid chromatography could be demonstrated.

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For the early diagnostics of chronic nonspecific pulmonary disease reversible functional disorders in persons without any symptoms and those with manifest obstruction should be identified. Provocation tests with acetylcholine-ultrasonic-aerosol have proved themselves. In 25 persons without any respiratory symptoms and in 27 patients with manifest obstruction the reactions of increased airway resistance to the hemodynamic of the pulmonary circuit were studied. It is possible to separate clearly groups with different pulmonary artery stream resistance measured by means of microheart-catheterization after inhalation of 0.01% acetylcholine-ultrasonic-aerosol.

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Investigations in 77 healthy persons and 94 patients with a manifest obstructive lung disease have led to the result that not only the central but also the peripheral part of the bronchial system are influenced by the bronchial reactivity. Accordingly the examination of the bronchial reactivity (0.01% acetylcholine solution as ultrasonic aerosol) enable in healthy persons a certain differentiation between smokers and non-smokers if the single breath test by means of the slope index are used. Therefore the method of investigation may be recommended for the early detection of functional disorders of persons with inhalatory exposure to noxious substances.

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The possibility of early detection of pulmonary hypertension is rather late according to the large capacity of the lung vessels in the condition of rest. Consequently the parameters of the pulmonary circulation were measured in 89 healthy subjects and 261 men suffering from silicosis in rest and bicycle exercise by means of the microcatheter technique and statistically compared with other parameters of lung function. In conclusion it can be said there is a statistical correlation between pressure at rest and during exercise conditions, but this is not available in an individual case. Furthermore the pressure values of persons suffering from silicosis are higher than those of the healthy group at rest and the pressure rise is higher in the ill group during exercise. Statistically there is a slight correlation between the pressure behavior and the FEV1, Rtot, PO2, DCO and of minor importance to VC, RC and FRC.

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The influence of hypobaric hypoxia at the pulmonary gaseous exchange and the hemodynamics of the pulmonary circulation was tested by 12 healthy subjects at the age from 33 to 47 years. They were submitted to a basis investigation with determination of VC, VE, VO2, VCO2, Hb, PO2A/a, pH, HR, ECG, PVd, PAp, HZV, RL. These investigations were followed by stress examination by means of the bicycle ergometry in four rectangular steps during conditions of normoxia and of hypobaric hypoxia in a low-pressure chambre at 66.5 kPa (500 Torr) each of 6 min duration. During the influence of hypoxia a PO2a-decrease in a sense of partial insufficiency could be already observed at rest during conditions of a decreased alveolar oxygen-partial-pressure. At the same time was found a significant increase of the systolic peripheral and the diastolic pulmonary arterial pressure. At the increasing step by step ergometric exercise during conditions of the hypoxia stress were growing significance evidence of different reactions of the pulmonary and cardiocirculatory parameters occurred.

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A great number of clinical and functional-diagnostic efforts are aimed at interpretation to the thorax-surgeon about the functional risk before a lung operation and to guarantee the patient with resected lung a sufficient pulmonal and cardial efficiency in the postoperative period of life. In a retrospective study 78 male patients were investigated with regard to the course of the ventilatory, respiratory and hemodynamic function until a postoperative interval of maximum 25 years, and differences in dependence on the operation-age are pointed out.

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To test the influence of hypoxia upon the pulmonary gaseous exchange and the hemodynamics of the pulmonary circulation 12 healthy test-persons at the age from 33 to 47 years (mean = 36.7 years) were submitted to a pulmonary and cardiocirculatory basis-investigation with determination of VK, VE, VO2, VCO2, Hb, PO2A/a, PCO2A/a, pH, BE, HR, ECG, PVd, PAp, SV, HZV, RL. These investigations were followed by stress examination by means of the bicycle-ergometry in four rectangular steps under conditions of normoxia from 95.5 to 97.3 kPa, x = 96.5 kPa (716 to 730 torr, mean = 723.6 torr) and of hypobarohypoxia in a low-pressure chambre at 66.5 kPa (500 torr) each of 6 min duration. Under the influence of hypoxia a PO2a-decrease in the sense of partial insufficiency could be already observed at rest under conditions of a decreased alveolar oxygen-partial-pressure. At this simultaneously increases the CO2-exhalation. At the same time was found a significant increase of the systolic peripheric and the diastolic pulmonary-arterial pressure. At the increasing step-by-step ergometric employment under conditions of the hypoxia stress were growing significance evidence of different reactions of the pulmonary and cardiocirculatory parameters occurred.

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As a task in the research project Chronic Lung Diseases the method of testing bronchial reactivity by provocation with acetylcholine as an ultrasonic aerosol was developed. Indications for an uniform standardized application and policy are given.

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Bronchial hyperreactivity (tested with 0.01% acetylcholine ultrasonic aerosol) and ventilatory inhomogeneity (tested with V2/V1-parameter of the flow-volume diagram) using the pneumotest apparatus were studied. Patients with high bronchial reactivity are frequently showing not only ventilatory disorders of distribution but sometimes also an additional increase due to the bronchial provocation. Bronchial reactivity testing combined with the flow-volume diagram allows to estimate the predominant site of the bronchospastic response either centrally or also in the more peripheral parts of the bronchial system. By testing bronchial reactivity persons without any symptoms and with no evident spirometric alterations can be separated in dependence on the relative increase of total airway flow resistance as well on smoking habits. That does not succeed with the appliance of the inhomogeneity parameters V2/V1. The results obtained in this study are of value for preventive measures, for early detection of risk factors in premorbid stages, for assessment of prognosis in chronic nonspecific lung disease, for an adequate therapy and also for the rehabilitation of patients in jobs with inhalation of noxious dusts.

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