Airway diseases and allergies in East and West German children during the first 5 years after reunification: time trends and the impact of sulphur dioxide and total suspended particles.

BACKGROUND: East-West comparison studies in Europe find higher prevalences of infectious airway diseases and lower prevalences of allergies in eastern areas. Pollution from sulphur dioxide (SO2) or total suspended particles (TSP) are discussed as causes of this difference. METHODS: In four differently polluted areas of East Germany where pollution decreased dramatically between 1989 and 1995 cross-sectional studies in about 7-year-old children were repeated every year between 1991 and 1995. In two differently polluted areas of West Germany studies with the same design were done in 1991 and 1994. In all, 19090 children participated in the study. Thirteen different questions about airway diseases and allergies were evaluated. Logistic regression was used to adjust for confounding. RESULTS: With the exception of pneumonia, all infectious airway diseases and irritations of the airways show a steeper temporal decrease in East than in West Germany or are positively associated with either SO2 or TSP in East Germany. For allergies and related symptoms no differences in time trends could be detected or no association with SO2 or TSP could be seen in East Germany. CONCLUSION: Most airway diseases were more frequent in East than in West Germany in 1991 and were associated with SO2 or TSP. The decrease in these pollutants between 1991 and 1995 has already had a favourable effect. An effect of SO2 or TSP pollution on allergies and related symptoms could not be detected. This pollution does not protect against the development of allergies.

Non-specific airway responsiveness to hyperventilation of low doses of sulfur dioxide and cold air of non-smoking healthy volunteers of different ages.

We examined the effect of hyperventilation (HV) of sulfur dioxide (SO2)-air and cold air for 5 minutes on airway responsiveness of 37 (12 females and 25 males) healthy non-smoking volunteers of different ages. Body-plethysmographic measurements of airway resistance (Raw) and intrathoracic gas volume (ITGV) were performed before, 3, 10 and 20 mins. after the end of HV of SO2-air or cold air. Specific airway resistance (sRaw), product of Raw x ITGV, was used to evaluate the airway responsiveness. The mean (standard error) of percent changes of sRaw (delta %sRaw) were 121 (22), 45 (8) and 25 (4) at 3, 10 and 20 mins. after the end of HV of SO2-air. The corresponding values were 52 (8), 25 (5) and 19 (3) after HV of cold air. The differences in delta %sRaw between HV of SO2 and cold air were statistically significant (two sided t-test) for the 3 (p < 0.01) and 10 (p < 0.05) mins. values. Hyperventilation of SO2 and cold air produced delta sRaw above 100% in 14 (37.8%) and 5 (13.5%) volunteers, respectively. The difference in frequencies of delta sRaw above 100% between the HV of SO2 and cold air was statistically significant (p < 0.05, chi 2-Test). We observed a decreasing order of airway responsiveness with increasing age following HV of SO2 but not after cold air. We conclude that airway responsiveness to SO2 is poorly related to the response to cold air.

[Evaluation of the use of an environmental medicine consulting center]. / Auswertung der Inanspruchnahme einer umweltmedizinischen Beratungsstelle.

At the Environmental Medical Consulting Centre 1677 consultations were carried out in 1991. The centre is established at the Medical Institute of Environmental Hygiene in Düsseldorf. There were 1129 (68%) short questions and 309 (18%) detailed consultations by phone or by letter. The most of the questions were asked by the general population. Other questions came from people at health offices, from general practitioners and from hospitals. No detail information about some socio-demographic data of this group was taken. The overwhelming topics of the questions were toxicological problems of harmful substances in indoor air or about the use of some products containing harmful substances. 239 (14%) people of the whole group got an appointment for a detailed medical consultation. Only data from 158 patients--visiting the office during January and September 1991--were evaluated in detail. On average the patients examined were 40 years old and mostly with a higher school degree. The most of the people complained about permanent polysomatic symptoms. A defined exposure was diagnosed for 31 (20%) patients, which resulted from pollution at work, at home or from the environment. The term Sick-Building-Syndrome were used for further 16 (10%) patients. In conclusion, the results of the study reveal a need of consultation with a specific orientation in Environmental Medicine. But, because of lack of data from other consulting offices in order to compare the results, no quantification of the need could be estimated.

Pulmonary alveolar proteinosis in rats after administration of quartz: its possible role in morphogenesis of lung cancer.

In rats, primary peripheral lung tumors composed predominantly of alveolar type II cells have been induced by inhalation of alpha quartz. In our retrospective study on proliferation markers we evaluated lung specimens of 140 Wistar rats from larger experiments, which had been exposed to Dörentrup quartz (DQ12) by inhalation (10 mg/m3, 56 Weeks, 5 days/week, 7 h/day: n = 27) or intratracheal instillations (5 mg: n = 38; 20 mg: n = 10; 50 mg: n = 28; 15 x 3 mg: n = 12). In the last group 8/12 animals developed lung tumors. Animals were sacrificed 1-32 months after administration. For identification of an increased proliferation of alveolar type II cells the DNA content was monitored by microscopic (static) cytophotometry in histological slides. The argyrophil (AgNOR) method for the demonstration of nucleolar organizer regions (NOR) was used as second marker of type II cell proliferation. Measurements made 24 months after inhalation of DQ12 showed a slight increase of pneumocytic proliferation with 1.64 +/- 0.14 AgNOR/nucleus compared to the controls (1.23 +/- 0.04 mean AgNOR/nucleus). After intratracheal instillation of DQ12 a significant increase of AgNOR was found, e.g. 5 mg: 1.93 +/- 0.23 AgNOR/nucleus (6 months) and 1.96 +/- 0.19 (12 months); 50 mg: 1.77 +/- 15 (6 months) and 2.18 +/- 0.05 (12 months); 15 x 3 mg (+2 ml 2% polyvinylpyridine N-oxide s.c.): 1.81 +/- 0.13 AgNOR/nucleus (27-32 months). With the aid of the 2 c deviation index, i.e. the mean square deviation from the diploid DNA value, it was possible also to identify the pathologically increased proliferation of type II cells after intratracheal instillation of quartz: 0.02 +/- 0.01-0.06 +/- 0.04 c2 (controls); 0.07 +/- 0.04 c2 (5 mg/12 months); 0.12 +/- 0.08 c2 (15 x 3 mg/>27 months) and 0.68 +/- 0.48 c2 (50 mg/12 months). Only in the last group were nearly triploid values detected. Summarizing our results, intratracheal instillation and inhalation of quartz in rats regularly induces alveolar proteinosis and interstitial fibrosis in combination with a dose- and time-dependent increase of the type II cell proliferation rate. As mitogenesis increases carcinogenesis, alveolar proteinosis with increased pneumocytic proliferative activity might be a prerequisite for enhanced tumor development.

[PATIS--a questionnaire-based, PC-assisted patient information system in the field of environmental medicine]. / PATIS--Ein Fragebogen-basiertes, PC-gestütztes Patienten-Informationssystem im Bereich Umweltmedizin.

PATIS was developed as a questionnaire-based, PC-assisted patient-information- and documentation-systems within the framework of the "Umweltmedizinische Beratungsstelle" (advisory board for clinical environmental medicine) at the Medical Institute of Environmental Hygiene at the Heinrich-Heine-University Düsseldorf. PATIS is a substantial element of a planed knowledged-based-system in environmental medicine. This system will further-more consist of databases for chemical substances information, exposition, and literature. PATIS records information about patients concerning personal data, former diseases, symptomatology and complaints, lifestyle, residential and working area, and spare time activities. Furthermore the state of physical examination, performances of diagnostics, and laboratory investigations are documented. A different questionnaire exists for children younger than 12 years. PATIS is able to supply an automatic report based on information of the questionnaire. This system is realized in the relational-database-system dBase IV and is utilized practice since the beginning of 1991.

[Dose-response pattern of inhaled sulfur dioxide (SO2) in rabbits pretreated with papain or sodium chloride aerosols]. / Dosis-Wirkungsmuster von inhaliertem Schwefeldioxid (SO2) an mit Papain- oder Kochsalz-Aerosol vorbehandelten Kaninchen.

The study was conducted on 29 New-Zealand female rabbits to examine the dose-response pattern of SO2 in inhaled air. A group of 14 animals was exposed to papain-aerosol (P-A) twice a week for 1 h each over 12 weeks in order to increase bronchial reactivity. A group of 9 animals received similar treatment but with saline-aerosol (NaCl-A); this group served for control. The third group of 6 animals remained untreated (K). After 12 weeks of treatment individual animals were anesthetized and the P-A and NaCl-A groups were exposed for 5 min each to different concentrations of SO2 (0.0, 1.0, 2.0, 4.0 and 9.0 mg/m3). The animals of group K were treated similarly but they were exposed 5X to synthetic air; this group served the purpose to follow the anesthesia effect on respiration and cardio-vascular system. The recovery period was 30 min between the exposures. The K-animals showed gradual decrease of lung resistance (R1). In contrast P-A and NaCl-A animals both showed a clear increase in R1 following exposure to SO2, and R1 was considerably higher in P-A than in NaCl-A animals. The maximum change in R1 was caused by exposure to 4.0 mg/m3 SO2 and it was even greater than the response produced by 9.0 mg/m3 SO2 in P-A animals. A similar pattern of response was also observed in NaCl-A animals, but the highest increase in R1 was caused by exposure to 2.0 mg/m3 SO2. From these results it can be concluded that high concentration of SO2 could have a damaging effect on sensory receptors of the tracheobronchial system.

[Carcinogenicity of glass fibers of different stability]. / Kanzerogenität von Glasfasern mit unterschiedlicher Beständigkeit.

A new type of fibrous glass showing a low durability in the body was injected intraperitoneally into rats. In the range of the doses applied (up to 10(9) of a thinner product and up to 0.24 x 10(9) of a thicker product) a carcinogenicity was not detected; in contrast, durable glass fibres induced tumours. It is recommended to use mineral fibres with low durability as far as possible.

[Status of lung function in females of a North Rhine-Westphalia rural and urban-industrial area]. / Lungenfunktionsstatus von Frauen in einem ländlichen und einem städtisch-industriellen Gebiet Nordrhein-Westfalens.

A comparative investigation of the pulmonary function status was carried out in women, aged between 52 and 56 years, from a rural and a municipal industrial area in North Rhine Westphalia. A questionnaire that the subjects had to complete themselves, provided us with information on personal medical history, smoking habits, the nature of domestic heating, and social status (education). The function tests were performed in a mobile pulmonary function laboratory (Jäger, Inc.). The airway resistance (Raw) and the intrathoracic gas volume (ITGV) were measured with the aid of a constant-volume body plethysmograph; a pneumotachographic system was employed to measure the ventilatory pulmonary function. All lung volumes were recalculated in terms of BTPS, and expressed as a percentage of the predicted values. Women from Leverkusen complained somewhat more frequently of hay fever, allergies of all kinds, and non-respiratory disturbances, than did women from Borken. In contrast, respiratory symptoms were indicated equally frequently in both areas. In the case of the Leverkusen group, a mean Raw of 0.323 +/- 0.183 kPa.1-1.s, was obtained, and in the case of the Borken group, a mean Raw of 0.258 +/- 0.182 kPa.1-1.s; this difference is statistically significant (p less than 0.05). On average, the women from Leverkusen also had a significantly higher SRaw (p less than 0.005) and ITGV (p less than 0.05) than did the women from Borken. These results argue in favour of a negative influence of air pollution on the pulmonary function.

Reversible fraction of airway resistance in healthy children of areas with different levels of atmospheric pollutants.

Reversible fraction of airway resistance (delta Raw) has been defined as the difference between airway resistances (Raw) before and after inhalative treatment with ipratropium-bromide (Atrovent) aerosols in healthy subjects. We examined delta Raw in children between 6-8 years of age living in areas with different air qualities. We found small but statistically significant (p less than 0.1) greater delta Raw for children of higher polluted areas. This could indicate that children of polluted areas possessed higher bronchial smooth muscle tone.

Animal experimental model for studying respiratory and cardiovascular parameters in unanaesthetized rabbits.

The purpose of the study was to examine the reproducibility of measurements of respiratory and cardiovascular functions in unanaesthetized rabbits. Observed coefficient of variations (CV) and hence the reproducibilities of different measurements in the present study were highly comparable to values reported for anaesthetized rabbits. So it could be concluded that anaesthetization is not a prerequisite to study respiratory and cardiovascular function in rabbits.

Cadmium in kidney cortex of inhabitants of North-West Germany: its relationship to age, sex, smoking and environmental pollution by cadmium.

The cadmium concentration in kidney cortex (CdKc) was determined in 388 deceased persons, who at the time of death had lived in the cities of Düsseldorf and Duisburg, Federal Republic of Germany (FRG), and surrounding areas. The average CdKc concentration was found to be 17.1 micrograms/g wet weight. Individual values range from less than 0.4 to 94.3 micrograms/g wet weight. The CdKc levels rapidly increase during the first decades of life. At the age of about 40 years, a plateau phase is reached. At high ages (greater than 70 years), the CdKc levels tend to decrease. Cigarette smokers have significantly higher CdKc concentrations than non-smokers. The increase of CdKc depends on the number of cigarettes smoked. Cigar and pipe smokers have slightly increased CdKc levels compared to non-smokers. Non-smokers who had spent the major part of their life in the area of Duisburg, a cadmium-polluted area, have, on the average, significantly higher CdKc levels than non-smokers from the less-polluted surrounding areas. In smokers the residential factor is masked by the effect of cigarette smoking.

[Cellular and molecular biological aspects in environmental toxicology]. / Zelluläre und molekularbiologische Aspekte in der Umwelttoxikologie.

Health effects of substances in the environment are considered from the viewpoint of cellular and molecular biology. There are nephrotoxic effects of cadmium to be discussed as well as mechanisms of carcinogenesis and neurotoxicity. Finally, the influences of noxious substances on lung clearance and immune reactions are demonstrated.

Growth and bone maturation in children from two regions of the F.R.G. differing in the degree of air pollution: results of the 1974 and 1984 surveys.

Growth and bone maturation criteria were used in this collaborative study to assess the potential health risk posed by excessive air pollutant emission. The study consisted of two surveys carried out 10 years apart. During this decade, a substantial emission reduction through the effective control efforts was achieved in the index area, but not so in the reference area where the situation remained virtually unchanged during this period. In terms of body height and height-weight proportionality, no significant differences were found between areas and years of investigation. In contrast, the bone age retardation encountered in the children from the polluted area was statistically significant, both at 1974 and 1984 surveys, despite the appreciable improvement in this developmental criterion for boys in 1984. This was true for both group mean values and the percentages of individuals exhibiting the bone maturation delay greater than 10 months.

[Health effects of air pollutants]. / Gesundheitliche Auswirkungen von Luftschadstoffen.

Air pollutants can exhibit both acute and chronic effects. Acute effects mainly occur during smog situations in industrial areas when atmospheric concentrations of hazardous substances are extremely high. This leads to an increase of morbidity and mortality especially in old and ill people. Chronic effects are the consequence of a longlasting exposition to low doses of noxious substances. Epidemiological studies have shown that frequency of respiratory diseases is higher in air polluted areas; this effect is particularly evident in smokers. Biological monitoring is used to determine the individual heavy metal burden. Lead is a danger especially for the developing central nervous system. Cadmium accumulates in the renal cortex during lifetime and may cause disturbances of renal function if a certain concentration is reached. The risk groups for heavy metals are young children and pregnant women in the case of lead and old people in the case of cadmium, respectively. Lung cancer incidence is higher in large cities than in rural areas. Carcinogenicity of city smog extracts was proved in vitro and in vivo. These findings suggest that urban air pollution may play a role as a causal factor in respiratory cancer.

[Polyvinylpyridine N-oxide (Bay 3504, P-204, PVNO) in the treatment of human silicosis]. / Polyvinylpyridin-N-Oxid (Bay 3504, P-204, PVNO) in der Behandlung der Silikose des Menschen.

After having demonstrated the therapeutic effectiveness of polyvinylpyridine-N-oxide (PVNO) for experimental silicosis in numerous animal studies, and after having finalized the toxicological examinations, a tolerance test was run in a controlled clinical assay with human subjects. After having shown that PVNO infusions did not result in toxic side-effects its therapeutic effectiveness was clinically studied in two different cohorts: matched pairs studies were conducted in 8 miners (group 1) and in 20 stone-cutters (group 2). The study demonstrates the therapeutic potency of PVNO for man as well, subject to certain moderating conditions as follows: the degree of silicosis, the age of the silicotic focus and the dust-type influenced the outcome of the treatment. The minimal dose should be between 300 and 400 mg per kg bodyweight and should be given in intervals of one to two years.

[Does an obturation in colorectal cancer also modify the behavior of the serum CEA level?]. / Beeinflusst eine Obturation beim kolorektalen Karzinom zusätzlich das Verhalten des CEA-Serumspiegels?

The CEA-plasma level was determined in 10 patients with malignant obstruction of the large intestine and in 6 patients with benign obstruction of the small intestine. The plasma carcinoembryonic antigen levels were obtained prior to initiating of the treatment and sequentially after treating the complete obstruction. Elevated plasma carcinoembryonic antigen levels are related to the carcinoembryonic antigen production by the primary tumour and not additionally to the obstruction. An elevated plasma CEA level in patients with benign obstruction could not be detected. After relief of obstruction, significant changes in the mean carcinoembryonic antigen values could not be observed.

The recognition of human bronchogenic carcinomas.

Xenotransplants of human carcinomas were tested for consistency of the analytical data of tumor markers over several passages in nude mice and nude rats. The binding properties of antibodies against tumor-associated antigens present in sera from tumor-bearing patients were tested with aid of the anticomplement immunofluorescence. The best binding capacity was found when sera from patients with bronchogenic carcinomas reacted on xenotransplants of the digestive tract (70%). Because of the low values for controls as well as for inflammatory diseases, this test may be applicable in the early recognition of lung cancer.