Lothar Kreienbrock

Radon in homes and risk of lung cancer: collaborative analysis of individual data from 13 European case-control studies

Abstract Objective To determine the risk of lung cancer associated with exposure at home to the radioactive disintegration products of naturally occurring radon gas Design Collaborative analysis of individual data from 13 case-control studies of residential radon and lung cancer. Setting Nine European countries. Subjects 7148 cases of lung cancer and 14 208 controls. Main outcome measures Relative risks of lung cancer and radon gas concentrations in homes inhabited during the previous 5-34 years measured in becquerels (radon disintegrations per second) per cubic metre (Bq/m3) of household air. Results The mean measured radon concentration in homes of people in the control group was 97 Bq/m3, with 11% measuring > 200 and 4% measuring > 400 Bq/m3. For cases of lung cancer the mean concentration was 104 Bq/m3. The risk of lung cancer increased by 8.4% (95% confidence interval 3.0% to 15.8%) per 100 Bq/m3 increase in measured radon (P = 0.0007). This corresponds to an increase of 16% (5% to 31%) per 100 Bq/m3 increase in usual radon—that is, after correction for the dilution caused by random uncertainties in measuring radon concentrations. The dose-response relation seemed to be linear with no threshold and remained significant (P = 0.04) in analyses limited to individuals from homes with measured radon < 200 Bq/m3. The proportionate excess risk did not differ significantly with study, age, sex, or smoking. In the absence of other causes of death, the absolute risks of lung cancer by age 75 years at usual radon concentrations of 0, 100, and 400 Bq/m3 would be about 0.4%, 0.5%, and 0.7%, respectively, for lifelong non-smokers, and about 25 times greater (10%, 12%, and 16%) for cigarette smokers. Conclusions Collectively, though not separately, these studies show appreciable hazards from residential radon, particularly for smokers and recent ex-smokers, and indicate that it is responsible for about 2% of all deaths from cancer in Europe.

Gender differences in lung cancer risk by smoking: a multicentre case-control study in Germany and Italy.

Several studies in the past have shown appreciably higher lung cancer risk estimates associated with smoking exposure among men than among women, while more recent studies in the USA report just the opposite. To evaluate this topic in a European population we conducted a case–control study of lung cancer in three German and three Italian centres. Personal interviews and standardized questionnaires were used to obtain detailed life-long smoking and occupational histories from 3723 male and 900 female cases and 4075 male and 1094 female controls. Lung cancer risk comparing ever-smokers with never-smokers was higher among men (odds ratios (OR) adjusted for age and centre = 16.1, 95% confidence interval (CI) 12.8–20.3) than among women (OR = 4.2, CI 3.5–5.1). Because the smoking habits of women were different from men, we conducted more detailed analyses using comparable levels of smoking exposure. After restriction to smokers and adjustment for other smoking variables, risk estimates did not differ appreciably between genders. The analysis of duration of smoking (0–19, 20–39, 40+ years) adjusted for cigarette consumption and time since quitting smoking revealed similar risk estimates in men (OR = 1.0, 3.3 [CI 2.6–4.2], 4.1 [CI 3.1–5.6]) and women (OR = 1.0, 2.7 [CI 1.7–4.1], 3.3 [CI 1.9–5.8]). The same was true of the analysis of average or cumulative smoking consumption, and also of analyses stratified by different histological types. We conclude that for comparable exposure to tobacco smoke, the risk of lung cancer is comparable in women and men.

Longitudinal Monitoring of Extended-Spectrum-Beta-Lactamase/AmpC-Producing Escherichia coli at German Broiler Chicken Fattening Farms

ABSTRACT Antimicrobial resistance of Escherichia coli to modern beta-lactam antibiotics due to the production of extended-spectrum beta-lactamases (ESBL) and/or plasmid-mediated AmpC beta-lactamases (AmpC) represents an emerging and increasing resistance problem that dramatically limits therapeutic options in both human and veterinary medicine. The presence of ESBL/AmpC genes in commensal E. coli from food-producing animals like broilers may pose a human health hazard. However, there are no data available concerning the prevalence of ESBL/AmpC-producing E. coli in German broiler flocks using selective methods. In this longitudinal study, samples were taken from seven conventional broiler fattening farms at three different times within one fattening period. Various samples originating from the animals as well as from their direct environment in the barn were investigated for the occurrence of ESBL/AmpC-producing E. coli. Average detection levels of 51, 75, and 76% in animal samples collected during the three samplings in the course of the fattening period demonstrate a colonization of even 1-day-old chicks, as well as a continuous significant (P < 0.001) increase in prevalence thereafter. The detection frequencies in housing environmental samples were relatively high, with an increase over time, and ranged between 54.2 and 100%. A total of 359 E. coli isolates were characterized by PCR and partly via the disc diffusion method. This study shows that prevalence of ESBL/AmpC-producing E. coli increases during the fattening period of the broiler flocks examined. Both colonized day-old chicks and contaminated farm environments could represent significant sources of ESBL/AmpC-producing E. coli in German broiler fattening farms.

Lung cancer in lifetime nonsmoking men - results of a case-control study in Germany.

Epidemiological studies of lung cancer among nonsmoking men are few. This case–control study was conducted among lifetime nonsmoking men between 1990 and 1996 in Germany to examine lung cancer risk in relation to occupation, environmental tobacco smoke, residential radon, family history of cancer and previous lung disease. A total of 58 male cases with confirmed primary lung cancer and 803 male population controls who had never smoked more than 400 cigarettes in their lifetime were personally interviewed by a standardized questionnaire. In addition, 1-year radon measurements in the living and bedroom of the subjects last dwelling were carried out. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Having ever worked in a job with known lung carcinogens was associated with a two-fold significantly increased lung cancer risk (OR = 2.2; Cl = 1.0–5.0), adjusted for age and region. The linear trend test for lung-cancer risk associated with radon exposure was close to statistical significance, demonstrating an excess relative risk for an increase in exposure of 100 Bq m−3 of 0.43 (P = 0.052). Nonsignificantly elevated effects of exposure to environmental tobacco smoke in public transportation and in social settings were observed. No associations with a family history of cancer or previous lung diseases were found. Our results indicate that occupational carcinogens and indoor radon may play a role in some lung cancers in nonsmoking men.

Prevalence and potential risk factors for the occurrence of cefotaxime resistant Escherichia coli in German fattening pig farms—A cross-sectional study

A cross-sectional study concerning farm prevalence and risk factors for the count of cefotaxime resistant Escherichia coli (E. coli) (CREC) positive samples per sampling group on German fattening pig farms was performed in 2011 and 2012. Altogether 48 farms in four agricultural regions in the whole of Germany were investigated. Faecal samples, boot swabs and dust samples from two sampling groups per farm were taken and supplemental data were collected using a questionnaire. On 85% of the farms, at least one sample contained cefotaxime resistant E. coli colonies. Positive samples were more frequent in faeces (61%) and boot swabs (54%) than in dust samples (11%). Relevant variables from the questionnaire were analysed in a univariable mixed effect Poisson regression model. Variables that were related to the number (risk) of positive samples per sampling group with a p-value <0.2 were entered in a multivariable model. This model was reduced to statistically significant variables via backward selection. Factors that increased the risk for positive samples involved farm management and hygienic aspects. Farms that had a separate pen for diseased pigs had a 2.8 higher mean count of positive samples (95%-CI [1.71; 4.58], p=0.001) than farms without an extra pen. The mean count was increased on farms with under-floor exhaust ventilation compared to farms with over floor ventilation (2.22 [1.43; 3.46], p=0.001) and more positive samples were observed on farms that controlled flies with toxin compared to farms that did not (1.86 [1.24; 2.78], p=0.003). It can be concluded, that CREC are wide spread on German fattening pig farms. In addition the explorative approach of the present study suggests an influence of management strategies on the occurrence of cefotaxime resistant E. coli.

Relevance of Campylobacter to public health—The need for a One Health approach

Campylobacter species belong to the most important foodborne bacteria which cause gastroenteritis in humans in both developed and developing countries. With increasing reporting rates, the public awareness towards Campylobacter infections is growing continuously. This strengthens the necessity to establish intervention measures for prevention and control of thermophilic Campylobacter spp. along the food chain, as in particular poultry and poultry meat represent a major source of human infections. An interdisciplinary One Health approach and a combined effort of all stakeholders are necessary to ultimately reduce the burden of campylobacteriosis cases in humans. Numerous studies point out, however, that at present a complete elimination of Campylobacter in the food chain is not feasible. The present aim should therefore be to establish control measures and intervention strategies to minimize the occurrence of Campylobacter spp. in livestock (e.g. poultry flocks) and to reduce the quantitative Campylobacter burden in animals and foods. To this end, a combination of intervention methods at different stages of the food chain appears most promising. That has to be accompanied by targeted consumer advice and education campaigns to raise the awareness towards Campylobacter infections.

Extended-spectrum beta-lactamases (ESBL)/AmpC beta-lactamases-producing Escherichia coli in German fattening pig farms: a longitudinal study

The presence of ESBL/AmpC-producing Enterobacteriaceae in healthy livestock, such as pigs, was frequently reported worldwide in the last years. The development and potential spread of these resistant microorganisms in farm animals is discussed critically. Therefore, the main objectives of this longitudinal study were to determine potential sources and prevalence dynamics of ESBL/AmpC-producing Escherichia coli in seven German ESBL/AmpC-positive conventional fattening pig farms in the course of the fattening period. Samples tested were taken at three different times within one finishing fattening period and included 20 individual faeces samples as well as various samples of the animals housing environment such as pooled faeces, boot swabs, dust and environmental swabs. In individual faeces average carriage levels of 45%, 29% and 36% at the three sampling times were accompanied by decreasing faecal counts from 2.97 x 10(4) cfu/g at the first to 2.17 x 10(3) cfu/g at the third visit. In the animals housing environment 47.6% of pooled faeces and boot swab samples respectively and 5.9% of environmental swabs but none of the dust samples were tested positive. Altogether 228 E. coli isolates were analysed by combination disc tests, PCR and partly via sequencing.Thereby, a novel gene bla(TEM-206) was detected. This study shows different detection levels of ESBL/AmpC-producing E. coli amongst the different farms and in the course of the fattening period. Pooled faeces and boot swab samples but not dust samples seem to be appropriate to assess the herd status of pigs with respect to ESBL/AmpC-producing Escherichia coli.

Zum Vorkommen von Extended-Spektrum- und AmpC-Beta-Laktamase-produzierenden Escherichia coli in Nutztierbeständen: Ergebnisse ausgewählter europäischer Studien

Extended-Spektrum-Beta-Laktamase (ESBL) und plasmidkodierte Cephamycinase (pAmpCs) produzierende Escherichia ( E.) coli in Nutztierbestanden sind in jungster Zeit Gegenstand einer erhohten wissenschaftlichen und gesellschaftlichen Aufmerksamkeit. In diesem Artikel werden ausgewahlte europaische Studien zum Vorkommen und den Risikofaktoren fur das Auftreten dieser Resistenzen zusammengefasst. Diese Studien sind durch ihre unterschiedliche Methodik nicht unmittelbar vergleichbar, dennoch kann insgesamt eine sehr hohe Pravalenz feststellt werden. Fur Broiler liegt die Betriebspravalenz bei uber 40 % und die Einzeltierpravalenz bei ca. 30 %. Fur schweinehaltende Betriebe schwanken die Ergebnisse zur Pravalenz sehr stark. So wurden Betriebspravalenzen von 1 bis 80 % und Einzeltierpravalenzen von 15 bis 100 % berichtet. Bei der Untersuchung rinderhaltender Betriebe spielen die Art des Betriebes sowie die jeweilige Lebensphase der Tiere eine wesentliche Rolle. So wurden die hochsten Pravalenzen bei Kalbern beobachtet, wahrend diese bei alteren Mastrindern deutlich geringer waren. Bei Milchkuhen wurden nach der Kalbung mehr positive Proben gefunden als davor. Die ermittelten Risikofaktoren fur das Auftreten ESBL/pAmpC-produzierender E. coli unterscheiden sich je nach Tierart. In verschiedenen Studien konnte ein Zusammenhang zwischen dem Auftreten ESBL-produzierender E. coli und Faktoren wie dem Einsatz von Antibiotika sowie Managementfaktoren, z. B. Mastdauer und Zukauf von Tieren unterschiedlicher Herkunfte, festgestellt werden. Zum jetzigen Zeitpunkt fehlen landerubergreifende systematische und standardisierte epidemiologische Untersuchungen zum Vorkommen von ESBL/ pAmpC-produzierenden E. coli in Nutztierbestanden. Um die weitere Verbreitung und die Effektivitat von Praventionsmasnahmen kontrollieren zu konnen, sind flachendeckende, speziesubergreifende Monitoring- und Surveillance-Systeme mit harmonisierter Methodik essenziell. Moderne, insbesondere sequenzbasierte Typisierungsverfahren konnen dabei weitere Informationen zur Aufklarung von Ubertragungswegen liefern.

Domestic radon and lung cancer—current status including new evidence from Germany

Abstract Background : Based on the studies in uranium miners as well as in the general population, domestic radon has been identified as the most important environmental risk factor for lung cancer. In the two recent case-control studies in West and East Germany, the lung cancer risk due to exposure to residential radon was investigated. Methods : From 1990 to 1997, incident lung cancer patients (histologically/cytologically confirmed) as well as a random sample recruited from the population (controls) were interviewed on their residential history, smoking, occupational exposure and other risk factors. Two charcoal canisters and two alpha track detectors (exposure time 3 days, 1 year, respectively) were placed in the present and former dwellings of participants. In the West German study, the evaluation included 1449 cases and 2297 controls; 1053 cases and 1667 controls were recruited in East Germany. Odds ratios (OR) were estimated in a conditional logistic regression model adjusting for smoking and for exposure to asbestos. Results : In the entire West German study area, no odds ratio different from one is found, whereas in the embedded radon-prone matching areas, a clear influence of exposure to radon on the lung cancer risk is observed. The adjusted odds ratios [95% CI] in the radon-prone areas based on the year-long measurement in the last dwelling amount to 1.57 [1.08, 2.27], 1.93 [1.19, 3.13] and 1.93 [0.99, 3.77] for 50–80, 80–140 and over 140 Bq/m 3 compared to 0–50 Bq/m 3 . In East Germany, a small influence of exposure to radon on the lung cancer risk is observed in the entire study area. The adjusted odds ratios are 0.97 [0.78, 1.21], 1.05 [0.81, 1.36] and 1.37 [0.97, 1.93] for 50–80, 80–140 and over 140 Bq/m 3 compared to 0–50 Bq/m 3 . Considering the exposure during the last 5 to 15 years in the present and past homes as well as time spent at home shows, odds ratios are similar to those mentioned above. Conclusions : The results in the West German radon-prone matching areas and in East Germany are compatible with recent studies from Sweden and England, with the result of a meta-analysis including eight important published studies, as well as with risk models from the analysis of cohorts of miners. Therefore, new evidence of an exposure–response relation within the population is found.

Evaluation of invalid vaccine doses in 31 countries of the WHO African Region

We examined (a) the fraction of and extent to which vaccinations were administered earlier than recommended (age-invalid) or with too short intervals between vaccine doses (interval-invalid) in countries of the World Health Organisation (WHO) African Region and (b) individual- and community-level factors associated with invalid vaccinations using multilevel techniques. Data from the Demographic and Health Surveys conducted in the last 10 years in 31 countries were used. Information about childhood vaccinations was based on vaccination records (n=134,442). Invalid vaccinations (diphtheria, tetanus, pertussis [DTP1, DTP3] and measles-containing vaccine (MCV)) were defined using the WHO criteria. The median percentages of invalid DTP1, DTP3 and MCV vaccinations across all countries were 12.1% (interquartile range, 9.4-15.2%), 5.7% (5.0-7.6%), and 15.5% (10.0-18.1%), respectively. Of the invalid DTP1 vaccinations, 7.4% and 5.5% were administered at childs age of less than one and two weeks, respectively. In 12 countries, the proportion of invalid DTP3 vaccinations administered with an interval of less than two weeks before the preceding dose varied between 30% and 50%. In 13 countries, the proportion of MCV doses administered at childs age of less than six months varied between 20% and 45%. Community-level variables explained part of the variation in invalid vaccinations. Invalid vaccinations are common in African countries. Timing of childhood vaccinations should be improved to ensure an optimal protection against vaccine-preventable infections and to avoid unnecessary wastage in these economically deprived countries.