Bakgrund: Rökning står för mer än vart tionde dödsfall i Sverige och hälften av alla långsiktiga rökare avlider av rökrelaterade sjukdomar. Lungcancer är den femte vanligaste cancersjukdomen i Sverige och orsakas i första hand av rökning. Kronisk obstruktiv lungsjukdom (KOL) orsakas också i första hand av rökning och är den tredje vanligaste dödsorsaken i världen. Fler kvinnor än män dör av KOL i Sverige men förklaringen till detta är oklar. Den komplexa kemiska blandningen som inhaleras vid förbränning av tobak orsakar negativa hälsoresultat, särskilt cancer och lungsjukdomar. Risken för och svårighetsgraden av många negativa hälsoeffekter orsakade av rökning kan variera beroende på om man själv är rökare eller bara exponeras för tobaksrök. Rökavvänjningen är potentiellt den mest effektiva av alla förbyggande åtgärder. Rökning påverkar också metabolisering av olika läkemedel. Nikotin är den beroendeframkallande substansen i tobak som orsakar abstinensbesvär. Rökfri tobak t.ex. snustobak orsakar också sjukdomar men i mycket mindre utsträckning än cigaretter. Syfte: Syftet med detta examensarbete var att ytterligare belysa kända hälsoproblem med rökning samt att beskriva eventuella ytterligare, tidigare okända, hälsoproblem. Metod: Detta arbete är en litteraturstudie baserat på 6 vetenskapliga artiklar. Resultat: Rökning ökar mortalitet och förkortar därmed livslängd. En stor del av dessa dödsfall orsakas av hjärt-kärl sjukdomar, kronisk obstruktiv lungsjukdom och många olika cancersjukdomar. Det finns ingen riskfri nivå av exponering för tobaksrök. Slutsats: Rökning ökar risken för alla typer av hjärt-kärl sjukdomar, låg födelsevikt för barn och många olika typer av cancer. Risken för pankreascancer i samband med rökning är relaterat till mängden av tobak som rökts dagligen. Minskning av antal rökta cigaretter per dag eller förpackningar per år har annars ingen större effekt på att minska risken för sjukdomar eller minska mortaliteten.

<p>The objective of the dissertation was to study the cabin environment, and identify personal and environmental risk factors, associated with symptoms, and perception of cabin air quality. Another objective was to study if ban of smoking, and increased relative air humidity on intercontinental flights, could have a beneficial health effect. The studies were performed among Scandinavian cabin crew in one Airline Company. Office workers from the same company served as controls. Exposure differed between cruise and non-cruise conditions. Air humidity was very low during intercontinental flights (3-8%). Concentration of moulds, bacteria, formaldehyde, and ozone was low. Tobacco smoking increased respirable particles in the cabin air, from 3 to 49 mg/m3, and increased cotinine in urine. The ETS-exposure was highest in the aft part of the cabin. Symptoms and environmental complaints were more common among flight crew than office workers. We could identify personal factors of importance, and certain conditions that could be improved, to achieve a better cabin environment. There was an association between symptoms and environmental perceptions and work stress, lack of influence on working condition, and a history of atopy. After ban on smoking in aircraft, there was a decrease of ocular and general symptoms, and increased tear-film stability in aircrew. Air humidification reduced headache and ocular, nasal, and dermal dryness symptoms, increased tear-film stability, and increased nasal patency. Our result indicates that ETS and low air humidity are important environmental factors in aircraft, and that atopy, and work stress could be significant risk factors for symptoms and environmental perceptions.</p>

The objective of the dissertation was to study the cabin environment, and identify personal and environmental risk factors, associated with symptoms, and perception of cabin air quality. Another objective was to study if ban of smoking, and increased relative air humidity on intercontinental flights, could have a beneficial health effect. The studies were performed among Scandinavian cabin crew in one Airline Company. Office workers from the same company served as controls. Exposure differed between cruise and non-cruise conditions. Air humidity was very low during intercontinental flights (3-8%). Concentration of moulds, bacteria, formaldehyde, and ozone was low. Tobacco smoking increased respirable particles in the cabin air, from 3 to 49 mg/m3, and increased cotinine in urine. The ETS-exposure was highest in the aft part of the cabin. Symptoms and environmental complaints were more common among flight crew than office workers. We could identify personal factors of importance, and certain conditions that could be improved, to achieve a better cabin environment. There was an association between symptoms and environmental perceptions and work stress, lack of influence on working condition, and a history of atopy. After ban on smoking in aircraft, there was a decrease of ocular and general symptoms, and increased tear-film stability in aircrew. Air humidification reduced headache and ocular, nasal, and dermal dryness symptoms, increased tear-film stability, and increased nasal patency. Our result indicates that ETS and low air humidity are important environmental factors in aircraft, and that atopy, and work stress could be significant risk factors for symptoms and environmental perceptions.

La present tesi avalua les diferències entre homes i dones quant a les característiques sociodemogràfiques i clínicopatològiques, procés diagnòstic, tractament i pronòstic en una sèrie de casos diagnosticats de novo de càncer de bufeta en 18 hospitals de 5 regions espanyoles (estudi EPICURO). També s'estudia l'associació entre tabac i risc de càncer de bufeta segons el sexe en un estudi agregat d'estudis cas-control europeus i nord-americans de càncer de bufeta.Es trobaren diferències entre sexes quant a la incidència de la malaltia, en algunes característiques anatomopatològiques dels tumors i quant a tractament. No es varen observar diferències entre sexes davant d'un mateix nivell d'exposició al tabac. També s'observaren diferències entre homes i dones quant al risc de recidivar i de progressar dels tumors vesicals superficials, però no en el risc de morir dels pacients amb tumors invasius. / The thesis evaluates differences related to sociodemographic and clinic-pathological characteristics, diagnostic tests, treatment and prognosis of bladder cancer patients newly diagnosed in 18 hospitals from 5 Spanish areas according to sex. The work also assess the association between tobacco and bladder cancer risk according to sex in a pooled analysis of case-control studies of bladder cancer from Europe and North America.Differences between sex concerning disease incidence, pathological characteristics and treatment were observed. The relative risk of bladder cancer associated with tobacco was similar in both sex. Differences between men and women were observed regarding risk of recurrence and progression of their superficial tumors but not regarding risk of death because of an invasive tumor.

Cystic fibrosis (CF) is the most common genetic disease affecting Canadian newborns (1 in 3,850) and is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. This gene encodes for CFTR, a phosphorylation-dependent ion channel localized at the apical membrane. Phosphorylation of CFTR by the cyclic adenosine monophosphate (cAMP)-dependent enzyme protein kinase A activates its activity, facilitating the transport of chloride and bicarbonate ions across the epithelial membrane. CFTR contributes to ion and airway surface liquid regulation, crucial for maintaining host defenses. The inheritance of CFTR mutations leads to a variety of respiratory complications, including impaired mucociliary clearance, excessive mucus production, persistent airway infections, and heightened inflammation, ultimately causing lung damage. While there is currently no cure for CF, the development of CFTR modulators, targeting the defective CFTR protein directly, has significantly improved the quality of life for many CF patients. Despite these advancements, many patients remain unresponsive to current treatment options. It has been well-established that combination therapies outperform monotherapies, emphasizing the need for alternative or complementary therapeutic strategies for CF management. Furthermore, CFTR dysfunction extends beyond CF and has been implicated in other respiratory diseases, such as chronic obstructive pulmonary disease, which is primarily linked to tobacco smoke exposure. This Ph.D. thesis explores a complementary therapeutic approach, targeting proteins within the CFTR-containing macromolecular signaling complex to elevate intracellular cAMP levels, thereby enhancing CFTR function. We hypothesized that synergistic use of cAMP modulators, alongside CFTR modulators, will serve as an effective therapeutic strategy for CF and other respiratory diseases. Collectively, our studies highlight the potential of cAMP and CFTR modulation as a therapeutic strategy for improving the treatment of CF and other respiratory diseases, warranting further investigation, offering insights for future studies, and contributes to the ongoing pursuit of improved combination treatments. / Dissertation / Doctor of Philosophy (PhD) / Cystic fibrosis (CF) is the most common genetic condition affecting Canadian newborns, caused by inheritance of mutations in the CF transmembrane conductance regulator (CFTR) gene. These mutations result in respiratory issues, including breathlessness, excess mucus, and susceptibility to infections, causing lung damage and premature death. Despite progress in CF drug development, some patients remain unresponsive to existing drug combinations, highlighting the need for new combinations to improve the quality of life for all CF patients. CFTR function is also compromised in other respiratory diseases like chronic obstructive pulmonary disease, a lung disease that shares many characteristics with CF and is mainly caused by tobacco smoke exposure. This Ph.D. thesis explores the effectiveness of a new drug strategy targeting proteins interacting with CFTR. By investigating drugs to complement existing treatments, we aim to improve CFTR function. This research offers a promising strategy to improve treatment for CF and other respiratory diseases.