Durch eine stärkere Einbeziehung deutscher Hausärzte in die Raucherentwöhnung soll die Versorgung von Rauchern flächendeckend verbessert werden. Inwiefern dieser Anspruch realisierbar ist, wird im Rahmen der "Smoking and Nicotine Dependent Awareness and Screening" (SNICAS) Studie überprüft. SNICAS ist eine zweistufige epidemiologische Punktprävalenzstudie [Stufe I (Vorstudie): Charakterisierung einer repräsentativen, bundesweiten Stichprobe von n = 889 Hausärzten; Stufe II: Stichtagserhebung an n = 28 707 unselektierten konsekutiven Patienten], an die sich eine regionale klinische Interventionskomponente anschließt. In diesem Beitrag werden Prävalenzraten des Rauchens, Aufhörmotivation und bisherige Aufhörversuche von Primärarztpatienten berichtet. Dargestellt werden Erkennens- und Interventionsraten von Rauchern durch Hausärzte, das ärztliche Interventionsverhalten sowie deren Einschätzung der Chancen und Barrieren von Raucherentwöhnung im Praxisalltag. Die Ergebnisse der Studie belegen ein großes Interesse der Hausärzte am Thema Raucherentwöhnung. Dennoch weisen niedrige hausärztliche Interventionsraten bei gleichzeitig hohen Prävalenzraten von Rauchen und Nikotinabhängigkeit auf ein beträchtliches Versorgungsdefizit. Als Ursachen hierfür werden neben ambivalenter Aufhörmotivation der Patienten strukturelle Barrieren diskutiert. Die Autoren fordern neue klinische Versorgungsmodelle, die ein abgestimmtes Zusammenspiel von Hausärzten mit anderen, auf Raucherentwöhnung spezialisierte Berufsgruppen fokussieren. / Through smoking cessation interventions, primary care physicians could play an important part in the treatment of smokers in Germany. In the "Smoking and Nicotine Dependent Awareness and Screening" (SNICAS) study, we examined whether this increased involvement of primary care physicians might be implemented. SNICAS is a two-stage epidemiological point prevalence study. In stage I (pre-study), a nationwide sample of 889 primary care doctors was characterized; in stage II, 28 707 unselected consecutive patients were assessed on the target day. The investigation was followed by regional clinical interventions. The present article contains our findings on the prevalence of smoking, the motivation to quit, and the history of quit attempts among primary care patients. Information will be provided on how frequently physicians recognize and treat smokers; what kind of interventions they offer; as well as how they judge the opportunities and obstacles for smoking cessation in routine care. Despite the high prevalence of smoking and nicotine dependence and the primary care doctors’ interest in treating smokers, insufficient interventions are provided. Reasons for this situation include, but are not limited to the patients’ ambivalent motivation to quit and structural barriers. Hence, new clinical models of health care with an improved cooperation between primary care physicians and other specialists in the field of smoking cessation seem necessary.

Tabakkonsum bei Jugendlichen und erwachsenen Risikopopulationen. Einflussfaktoren und Ansätze zu Prävention und Intervention Die vorliegende Arbeit beschäftigt sich mit den Einflussfaktoren des Tabakkonsums bei verschiedenen Zielgruppen sowie möglichen Ansätzen zur nachhaltigen Beeinflussung des Rauchverhaltens. Die Arbeit besteht aus insgesamt sechs Manuskripten, die in nationalen und internationalen Fachzeitschriften publiziert oder zur Publikation angenommen sind. Diese sechs Beiträge lassen sich zwei Schwerpunkten zuordnen, die inhaltlich die zwei wichtigsten Möglichkeiten zur Reduktion des Tabakkonsums in der Bevölkerung widerspiegeln: die Verhinderung des Neueinstiegs in das Rauchen bei Kindern und Jugendlichen (Prävention) sowie die Förderung des Ausstiegs aus dem Rauchen (Intervention). Im ersten Teil wird im Rahmen eines Reviews sowie zweier Studien untersucht, ob sich verhältnispräventive Maßnahmen an Schulen auf das Rauchverhalten der Schüler auswirken. Im zweiten Teil untersuchen drei Studien die Motivation zur Verhaltensänderung, die Inanspruchnahme von Hilfsangeboten bzw. die Effektivität von Tabakentwöhnung bei Rauchern mit einer Alkoholabhängigkeit, Müttern in der Mutter-Kind-Rehabilitation sowie Patienten mit tabakassoziierten körperlichen Erkrankungen. / „Smoking in adolescents and adult risk populations. Factors of influence and approaches concerning prevention and intervention” This dissertation is concerned with factors influencing the smoking behaviour of different target groups and potential approaches for lasting changes of these behaviours. The dissertation consists of six manuscripts that are published or accepted for publication in national and international peer-reviewed journals. These six papers refer to two main emphases that reflect the two most important possibilities to reduce tobacco consumption in the population: Prevention of smoking initiation in children and adolescents (prevention), and support for smoking cessation (intervention). In the first part of the dissertation, a literature review and two empirical studies assess the influence of school tobacco policies on the smoking behaviour of students. In the second part, three empirical papers examine motivation to change, utilisation and effectiveness of smoking cessation in smokers with an alcohol dependence, mothers in mother-child rehabilitation and patients with smoking-related physical diseases.

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Hintergrund / Ziel der Studie: Im Bereich der Tabakentwöhnung existieren mittlerweile zahlreiche erprobte therapeutische Maßnahmen und Medikamente. Dennoch ist die Inanspruchnahme vorhandener Entwöhnungsangebote sehr dürftig. Es besteht die begründete Hoffnung, dass durch eine stärkere Einbeziehung der Hausärzte in den Bereich der Tabakentwöhnung eine Versorgungslücke geschlossen werden könnte. Die Studie soll Durchführbarkeit und Erfolg einer solchen Ausweitung des Anbieterkreises von Tabakentwöhnungsmaßnahmen im Hausarztbereich untersuchen. Unterschiedliche bereits vorhandene Therapieansätze werden hierbei hinsichtlich Effektivität und Effizienz in der allgemeinärztlichen Routineversorgung miteinander verglichen. Methoden: In Phase I der Studie werden bundesweit Patienten in mehr als 800 Arztpraxen an einem Stichtag per Fragebogen zu ihrer Gesundheit und ihrem Rauchverhalten befragt. In Phase II werden die in Phase I identifizierten entwöhnungswilligen Raucher in ausgewählten Arztpraxen für die Intervention rekrutiert und randomisiert vier Gruppen mit (idealerweise) jeweils 250 Personen zugeteilt: einer Bupropion SR (Zyban®)-Gruppe, einer Nikotinersatzmittel-Gruppe, einer Verhaltenstherapie-Gruppe und einer Kontrollgruppe. Die Behandlung erfolgt jeweils durch die Ärzte in ihren Praxen unter Supervision und mit Unterstützung durch Studienmonitore. Erwartete Ergebnisse: In Abhängigkeit von Merkmalen des Arztes und seiner Praxis auf der einen Seite sowie Merkmalen der betroffenen Patienten auf der anderen, sollte die Akzeptanz, Durchführbarkeit und Wirksamkeit der ausgewählten Therapieansätze unterschiedlich ausfallen. Insgesamt sollte jedoch jede Therapiebedingung gegenüber der Kontrollbedingung hinsichtlich ihrer Effektivität überlegen sein. Im 6-Monats Follow-up sollte die Zyban-Gruppe gegenüber allen anderen Gruppen die höchste Abstinenzquote aufweisen. Schlussfolgerung: Die Ergebnisse sollten Hinweise auf Möglichkeiten einer bedarfsgerechten, optimierten Allokation vorhandener Maßnahmen zur Tabakentwöhnung in der allgemeinärztlichen Versorgung liefern. / Background / aim of the study: Although a number of efficacious smoking cessation measures and medications do exist, only a small number of smokers (tobacco users) make use of them. A stronger engagement of general practitioners (GPs) in the field of smoking cessation might help to improve health care in this important area. The study will investigate feasibility and effectiveness of different readily available smoking cessation measures under routine conditions in primary health care practices. Method: In phase I of the study patients' health status and tobacco consumption are assessed by means of questionnaires provided on a nationwide appointed date in more than 800 general practices in Germany. In phase II selected practices offer smoking cessation treatments to identified smokers. Participants recruited will be randomly assigned to four groups ideally consisting of 250 subjects each: A bupropion SR (Zyban©) condition, a nicotine replacement therapy (NRT) group, a cognitive-behavioural treatment (CBT) group and a control condition. Treatments will be conducted by GPs in their practices under supervision of study monitors offering therapeutical and organisational support. Expected results: Acceptance, feasibility, and effectiveness of smoking cessation treatments offered will differ depending on GP and patient characteristics. Overall, success-rates (while success is primarily defined as abstinence from tobacco use) should be higher in all therapeutic conditions as compared to controls. In the 6-month follow-up abstinence rates are expected to be highest in the bupropion SR group. Conclusion: Results should yield indications for an improved allocation of available smoking cessation measures in primary care.

The associations between maternal smoking and nicotine dependence and patterns of smoking and nicotine dependence in offspring were examined in a large community-based sample of adolescents. Data were derived from baseline and 4-year follow-up assessments of 938 respondents aged 14–17 years at the outset of the Early Developmental Stages of Psychopathology (EDSP) study, a prospective-longitudinal community study of adolescents and young adults and their parents respectively. Smoking and nicotine dependence in respondents were assessed using the Munich Composite International Diagnostic Interview (DSM-IV algorithms). Diagnostic information about smoking behavior in mothers was collected by independent direct diagnostic interviews with the mothers. In comparison to children of non- or occasionally smoking mothers, children of regularly smoking and nicotine-dependent mothers had higher probabilities of using tobacco as well as of developing nicotine dependence. For all ages under consideration, survival analyses revealed a higher cumulative lifetime risk of regular smoking and nicotine dependence among these children. Maternal smoking during pregnancy seems to represent an additional risk for these outcomes in children, specifically with regard to the risk of developing nicotine dependence. Associations were comparable for sons and daughters. Our findings show that maternal smoking predicts escalation of smoking, development of nicotine dependence, and stability of smoking behavior in children. Implications for specific intervention and prevention efforts are discussed.

In den Industrieländern stellen arteriosklerotische Erkrankungen nach wie vor die häufigste Todesursache dar, noch vor den malignen Erkrankungen. Ziel dieser Studie war es auzuzeigen, in wie weit eine besonders intensive Betreuung und Aufklärung der Patienten bereits in der Akutphase während des stationären Aufenthaltes im Rahmen einer Herzbypass-Operation zu besseren Langzeitergebnissen (1-und 3-Jahres-follow-up) bezüglich der Reduktion von kardiovaskulären Risikofaktoren führt.

Die Rationale für immuntherapeutische Ansätze zur Behandlung maligner Neoplasien geht davon aus, daß Tumore über spezifische Tumorantigene verfügen. Dendritische Zellen als die wichtigsten antigenpräsentierenden Zellen sind in der Lage, Tumorantigene naiven T-Zellen zu präsentieren und spezifische zytotoxische T-Zellen zu stimulieren. In der vorliegenden Arbeit wurden dendritische Zellen durch Stimulation mit Interleukin-4 (IL-4) und Granulozyten/ Makrophagen Koloniestimulierender Faktor (GM-CSF) aus peripheren mononukleären Blutzellen gesunder Spender und an Tumoren des gastroenteropankreatischen Systems erkrankter Patienten generiert. Mit den dendritischen Zellen cokultivierte immunologische Effektorzellen (Zytokin- induzierte Killerzellen, CIK-Zellen) wurden im Zytotoxizitätstest gegen kolorektale und pankreatische Karzinomzellen eingesetzt. CIK-Zellen sind zytototoxische Zellen, die durch Stimulation mit Zytokinen aus peripheren Blutlymphozyten erzeugt werden. Durch die Cokultivierung der Effektorzellen mit dendritischen Zellen konnte eine signifikante Steigerung der unspezifischen zytotoxischen Wirkung der CIK-Zellen bewirkt werden. Zur Steigerung der spezifischen Zytotoxizität wurden dendritische Zellen mit dem Gesamtprotein der tumor- assoziierten Antigene cancer associated antigen (CA 19-9) und carcinoembryonic antigen (CEA) gepulst. Effektorzellen zeigten nach der Cokultur mit gepulsten dendritischen Zellen zytotoxische Wirkung gegen Targetzellen, die das zum Pulsen verwendete Tumorantigen auf der Zelloberfläche exprimieren. Die Antigenspezifität der zytotoxischen Wirkung konnte durch eine signifikant verminderte Zellyse nach Blockade des Tumorantigens auf den Targetzellen belegt werden. Erstmals beschrieben ist hier das Pulsen dendritischer Zellen mit sowohl autologen als auch allogenen Seren von Patienten mit erhöhten Tumormarkerspiegeln. Eine Kultivierung dendritischer Zellen in tumormarkerhaltigem Serum bewirkte dosisabhängig eine verstärkte zytotoxische Wirkung cokultivierter Effektorzellen gegen Tumorzellen. Die verstärkte Zellyse zeigte sich unabhängig vom allogenem oder autologem Charakter des Serums. Der immunstimulierende Effekt des Patientenserums konnte durch eine vorhergehende Hitzeinaktivierung des Serums neutralisiert werden. Die höchsten Zellysen wurden durch eine Kultivierung dendritischer Zellen in tumormarkerhaltigem Serum und zusätzlichem Pulsen mit exogenem Tumorantigen erreicht. Untersuchungen an komplett autologen Systemen reproduzierten die an Zellkulturen erhobenen Befunde. Hierfür wurden erfolgreich Primärkulturen kolorektaler Tumore etabliert.Aus dem Blut von Tumorpatienten wurden dendritische Zellen generiert, die mit autologem Serum kultiviert wurden. Die cokultivierten autologen Effektorzellen erwiesen sich im Zytotoxizitätstest gegen autologe Tumorzellen als zytotoxisch. Die Cokultivierung der Effektorzellen mit den dendritischen Zellen bewirkte bei beiden Zellpopulationen Veränderungen. Dendritische Zellen zeigten nach der Cokultur eine verstärkte Expression antigenpräsentierender und costimulatorischer Moleküle. Bei den CIK-Zellen kam es zu einem Anstieg der Proliferationsrate. Bei Untersuchungen zur Antigenspezifität von T-Zellrezeptoren konnte vermehrt antigenspezifischer T-Zellrezeptor nachgewiesen werden. Des weiteren stieg das Verhältnis zwischen zytotoxischen T-Zellen und T-Helferzellen zugunsten der zytotoxischen T-Zellen. In ELISpot-Untersuchungen wurde eine Zunahme Interferon-gamma sezernierender CIK-Zellen nachgewiesen. Dendritische Zellen ließen sich erfolgreich mit inaktiviertem Adenovirus, an das kovalent Poly-L-Lysin gekoppelt ist, transfizieren. Die für den adenoviralen Gentransfer benötigten Oberflächenstrukturen konnten auf dendritischen Zellen nachgewiesen werden. Zur Verbesserung der Zytotoxizität wurden dendritische Zellen erfolgreich mit dem Gen für den Transaktivator CIITA transfiziert. CIITA- transfizierte dendritische Zellen exprimierten vermehrt MHC Klasse II-Moleküle. Die transduzierten dendritischen Zellen induzierten bei cokultivierten Effektorzellen eine erhöhte unspezifische Zytotoxizität. Mit Tumorantigen gepulste dendritische Zellen können bei der Entwicklung immuntherapeutischer Protokolle bei malignen Neoplasien von Bedeutung sein. / The immunotherapeutic approach against malignant neoplasias appreciates that tumours encode tumour rejection antigens, that enable them to induce protective immunity. Dendritic cells are major antigen-presenting cells and are able to present tumour antigens to naive T-cells and stimulate cytotoxic T-cells in a specific manner. In the present graduation-manuscript dendritic cells were generated in the presence of Interleukin-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF) from peripheral mononuclear blood cells of healthy donors and tumour-patients. Immunological effector cells termed cytokine-induced killer cells (CIK cells) were co-cultured with dendritic cells and tested for their cytotoxic capacity against colorectal and pancreatic cancer cell-lines in a LDH-release assay. CIK cells are cytotoxic lymphocytes generated by incubation of peripheral blood lymphocytes with different cytokines. Co-culture of effector cells with dendritic cells led to a significant increase of the cytotoxic effect of CIK cells. For a further increase of specific cytotoxicity dendritic cells were pulsed with total protein of the tumour-associated antigens cancer associated antigen CA 19-9 and carcinoembryonic antigen (CEA). Co-cultured effector cells showed an increase in cytotoxicity against tumour-antigen expressing target cells, after co-culture with pulsed dendritic cells. The specificity of the cytotoxic effect could be shown by blocking the tumour-antigens with a monoclonal antibody. Autologous and allogenec untreated serums from patients with elevated tumour-marker levels were also used for pulsing of dendritic cells. Similar to the results when using total protein for pulsing, a cultivation in serum of patients with elevated tumour marker levels caused an intensified cytotoxic effect of effector cells against tumour cells in a dose-dependent manner. The intensified cytotoxicity was seen independent of the allogenec or autologous character of the serum. The immuno-stimulating effect of the patient serum could be neutralized by preceding heat inactivating. The highest cytotoxicity was achieved by a cultivation of dendritic cells in serum from patients with elevated tumour marker levels and additional pulsing with exogenous tumour antigen. Experiments with completely autologous systems reproduced the results made with cell-lines. Primary cultures of colorectal tumours were established. Dendritic cells were generated from the blood of tumour patients and were cultivated in autologous serum. Co-cultured autologous effector cells showed cytotoxicity when used against autologous tumour cells. Co-culturing of effector cells with dendritic cells caused modifications at both cell populations. Dendritic cells showed an increase expression of antigen-presenting and co-stimulatory molecules. CIK cells showed a higher proliferation-rate when co-cultured. They express more antigen-specific T-cell receptor, and the cytotoxic T-cells to T-helper cells ratio increased. ELISpot-assays showed an increase of interferon gamma producing cells. Dendritic cells were successfully transduced by using an inactivated adenovirus, which covalently binds poly-L-lysine. Dendritic cells express the molecules that enables adenoviral gene delivery on their surface. For the improvement of cytotoxicity dendritic cells were transduced with the gene encoding for the transactivator CIITA. CIITA transduced dendritic cells increases expression of MHC class II molecules. Cytotoxicity experiments with transduced dendritic cells resulted in an increased induction of non-specific cytolysis from co-cultured effector cells. DC pulsed with tumour-antigens may have a major impact on immunotherapeutic protocols for cancer patients.

Human decision making is closely related to reward processing because many decisions rely to a certain degree on the evaluation of different outcome values. Reward-based decisions can be health-related, for example if someone has to compare the outcome value of the instant reward of smoking a cigarette to that of the long term goal of keeping well and fit. Such comparisons do not only rely on the nominal value of the alternatives but also on devaluation of rewards over time. The value of being healthy at older age might outweigh the value of smoking a cigarette but since the payoff of the health-outcome will be delayed, humans tend to decrease the value of this option. Therefore in this example one might choose the immediate reward of smoking a cigarette. The proclivity to devaluate the value of rewards over time has been widely investigated with experimental intertemporal choice tasks, in which subjects have to choose between smaller sooner rewards and larger later rewards. A stronger individual devaluation proclivity (i.e. discounting rate) has been reported to be related to addiction. Research in neuroeconomics has suggested the competing neurobehavioural decision systems (CNDS) theory, proposing that an imbalance between an executive (cortical prefrontal brain areas) and an impulsive (i.e. subcortical areas, such as ventral striatum (VS), amygdala) system in the brain leads to steeper discounting and a higher risk for addiction. Additionally, temporal discounting has been proposed as a transdisease process, i.e., “a process that occurs across a range of disorders, making findings from one disorder relevant to other disorders” (Bickel, Jarmolowicz, Mueller, Koffarnus, & Gatchalian, 2012, Abstract). Thus, the CNDS theory and temporal discounting might also have implications for other health-related behaviour than substance use. So far many factors have been shown to be associated with higher discount rates: for instance, adolescent age, lower intelligence and nicotine dependence. Further, it has been shown that adolescents are at highest risk to start smoking. On the other hand a higher education level has been shown to be associated to lower rates of smoking. Thus, it seems likely that a higher discount rate might be one reason why adolescents experiment with smoking, why lower education is associated to nicotine addiction and why dependent smokers are not successful in smoking cessation. But relatively little is known about the neural processes behind these variables, which could be also seen as exemplary risk- and protective factors regarding addiction. The 3 studies of the thesis at hand were conducted to extend the knowledge about neural processes associated to age, intelligence and smoking in their relation to intertemporal choice. The task was chosen because of its relevance for addiction and a variety of health-related behaviour. The first study was conducted to explore the neural correlates of age related differences between adolescents at age 14 and young adults during intertemporal choices. Additionally, the roles of discounting and choice consistency were investigated. Although adoles-cents discounted delayed rewards more steeply than adults, neural processing of reward value did not differ between groups, when controlling reward values for the individual discount rates. However, a higher discount rate was related to a lower responsivity in the ventral striatum to delayed rewards, independent of age. Concerning decision making, adolescents exhib-ited a lower consistency of choices and less brain activity in a parietal network than adults (i.e. posterior and inferior parietal regions). Thus, reward value processing might be more sensitive to the discount rate than to chronological age. Lower consistency of intertemporal choices might indicate ongoing maturation of parietal brain areas from adolescence to young adulthood. The second study was conducted to reveal the associations between neural processes of decision making and intelligence in adolescents. The results of study 2 revealed networks in the adolescent brain where brain activity was related to crystallised intelligence as well as to intertemporal choice behaviour. Specifically, during decision processing higher crystallised intelligence as well as more consistent decisions were associated with higher brain activity in the posterior parietal cortex. Processing of delayed rewards was also related to crystallised intelligence, i.e. more intelligent adolescents showed higher brain activation in the anterior cingulate cortex (ACC) and the inferior frontal gyrus (IFG), which was in turn related to a lower discount rate. Additionally, associations between the parental education level and crys-tallised intelligence of the adolescent participants of the study and their discount rate were found, indicating that parental education as an environmental factor could be related to a low-er risk for addiction. This protective effect might be mediated by the offspring’s crystallised intelligence and discount rate which are both related to brain activity in parts of the same brain networks (i.e. the IFG). The third study was done to investigate neural processes of intertemporal decisions in smokers and non-smokers. To test whether the effects of smoking on the discount rate are due to chronic or acute nicotine intake, non-smokers were additionally assessed under acute nico-tine administration. Study 3 revealed that the effects of nicotine on intertemporal choice behaviour were related to chronic intake of nicotine in smokers rather than to acute nicotine ad-ministration in non-smokers. Regarding the neural processes, smokers compared to non-smokers showed lower brain activity in the posterior parietal cortex. Comparable but weaker effects were found under acute nicotine in non-smokers. Although acute nicotine administra-tion altered neural processes, behavioural changes might only occur after repeated nicotine intake. However, the study did not preclude that the differences are predrug characteristics. Altogether the studies revealed overlapping neural correlates of intertemporal choices which are related to the individual age, the discount rate, the choice consistency, the individual intelligence as well as acute and chronic nicotine intake. This might provide an integrative view on how inter-individual differences and behaviour during intertemporal choices are based on common neural correlates which in turn might have implications for the development and the maintenance of addiction. Specifically, hyposensitivity towards delayed rewards in the adolescent ventral striatum, which has also been found in smokers compared to non-smokers, is associated with higher discount rates and higher risk for smoking initiation. In contrast, higher activation in the IFG and the ACC in more intelligent individuals during reward value processing might enhance behavioural inhibition and control and, hence, might prevent nicotine addiction. In line with the CNDS theory responsivity in subcortical brain areas (i.e. impulsive system), such as the VS was related to the risk factor of adolescent age, whereas activity in cortical areas (IFG and ACC) was related to the protective factors of high-er crystallised intelligence. Since there was only one study beside the studies of the current thesis reporting results regarding consistency, one can only speculate about implications for health-related behaviour, such as addiction. Consistency might play a role, especially for cessation success. Thus, the findings that adolescents as well as less intelligent individuals were less consistent might point to a higher risk for maintenance of nicotine addiction. The higher brain activity in a fronto-parietal network, which has been shown in studies 1 and 2 in adults as well as in more intelligent adolescents, was related to higher consistency of choices in both studies. Thus, the finding might be a possible neural correlate for the association between the risk factor of ado-lescent age, the protective factor of higher crystallised intelligence, and more consistent deci-sion making. In conclusion the findings of the current thesis contribute to a better understanding of how inter-individual differences and environmental factors might be accompanied by neural processes which in turn might be related to individual development of addiction. Further the results might extend the CNDS theory regarding neural correlates of exemplary risk and pro-tective factors regarding adolescents’ health behaviour and smoking in adults.

Unter den bösartigen Tumoren hat das Bronchialkarzinom wohl die dramatischste Entwicklung genommen. Die Inzidenz und Mortalität ist in den letzten 15-20 Jahren bei Männern zwar leicht rückläufig, für Frauen ist jedoch ein entgegen gesetzter Trend zu erkennen. Dies wird in erster Linie auf die veränderten Lebensgewohnheiten, wie steigender Zigarettengenuss unter den Frauen, zurückgeführt. Derzeit gibt es in Deutschland circa 20 Millionen Raucher, von denen etwa 140˙000 jährlich an den Folgen ihres Inhalationsrauchens versterben...

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