Diss. (sammanfattning) Stockholm : Karolinska institutet, 2001. / Härtill 5 uppsatser.

Syftet med denna uppsats är att utröna om risken att avlida i förtid var större i Falun än på tre andra jämnstora orter i Mellansverige med i övrigt likartade miljömässiga förutsättningar, mellan åren 1750 till 1770. Det använda källmaterialet är Tabellverkets folkbokförings- och mortalitetstabeller för åren 1750 till 1770. Dödsfall i miljörelaterade sjukdomar för Falun har jämförts med orterna Mora, Gefle och Hedemora. Miljön i Falun skiljde sig från de andra orterna främst på grund av den massiva exponeringen av svaveldioxid och metallhaltiga partiklar, som förekom som ett resultat av gruvverksamheten och den efterföljande kopparframställningen. Gefle var en tätort med stadens problem medan Mora var ett agrart samhälle och Hedemora var både och. Resultatet visar, att risken att avlida i bröst- och lungrelaterade sjukdomar var signifikant högre i Falun än i Mora och Hedemora. Även i Gävle var risken mindre än i Falun, dock ej lika tydligt, vilket sannolikt är en följd av att Gävle var en tätort, som allmänt gav en högre dödlighet. Även den allmänna risken att avlida i förtid var högre i Falun än för de andra orterna. Undersökningen visar också på den risk, som fanns, att avlida i förtid, som de olika epidemierna gav upphov till och den stora inverkan det får. Medelåldern var högre i Falun än för de andra undersökta orterna men detta förklaras främst och rimligast av demografiska skillnader

Background: Childhood asthma has increased worldwide, although recent studies report a prevalence plateau in some western countries. Aims: To investigate the prevalence of asthma and the associated risk factor patterns from ages 7-8 to 11-12 with special emphasis on the hereditary component, and further to study prevalence trends at age 7-8 from 1996 to 2006 and the possible determinants of these trends. Methods: The studies involved two cohorts from Kiruna, Luleå and Piteå: one previously identified cohort of 3430 children age 7-8 followed by yearly questionnaires until age 11-12 with 97% yearly participation. Skin-prick tests for allergic sensitisation were performed at ages 7-8 and 11-12 in subsets of 2148 and 2155 children respectively (88% of invited). In 2006 a new cohort of 7-8-year-olds was identified and examined identically. 2585 (96% of invited) and 1700 (90% of invited) participated in the questionnaire and skin-prick tests, respectively. The questionnaire included questions about symptoms of asthma, allergic rhinitis and eczema, and possible risk factors. Results: In the 1996 cohort, from age 7-8 to 11-12 the prevalence of physician-diagnosed asthma increased (5.7%-7.7%, P<0.01) while current wheeze decreased (11.7%-9.4%, P<0.01), and 34.7% reported ever wheee at ≥one occasion. Remission was 10% of which half relapsed during the study. Remission was significantly lower among sensitised children. The strongest risk factors for current asthma at ages 7-8 and 11-12 were allergic sensitisation (OR 5) and family history of asthma (OR 3). Several other significant risk factors, e.g. respiratory infections, damp house and low birth weight, had lost importance at age 11-12. At age 7-8, parental asthma was a stronger risk factor (OR 3-4) than parental rhinitis or eczema (OR 1.5-2). Sibling asthma had no independent effect. Biparental asthma had a multiplicative effect (OR 10). Maternal and paternal asthma was equally important, regardless of the child’s sex and sensitisation status. From 1996 to 2006 the prevalence of current wheeze and asthma at age 7-8 did not increase (P=0.13, P=0.18), while lifetime prevalence of ever wheeze and physician-diagnosed asthma increased (P<0.01, P=0.01). Symptoms of rhinitis and eczema were unchanged, despite 45% increase (P<0.01) in allergic sensitisation. For current asthma the adjusted population attributable fractions of sensitisation and parental asthma increased (35%-41%, 27%-45%). This was however balanced by decreased exposure to infections, maternal smoking and home dampness, resulting in stable asthma prevalence. Stratification by sex revealed that current wheeze increased in boys (P<0.01) but tended to decrease in girls (P=0.37), seemingly due to symptom persistence in males. Several asthma indices followed this pattern. The boy-to-girl ratio in exposure to all studied risk factors increased, which may explain the sex-specific prevalence trends in wheeze. Conclusions: The prevalence of current asthma and wheeze did not increase statistically significantly. However, the risk factor pattern has changed considerably since 1996, which will presumably affect the clinical features of childhood wheeze in this region. Sex-specific trends in wheeze can be explained by changes in exposure, and trends in risk factors should be explored parallel to prevalence trends.

<p>Bakgrund: Kronisk obstruktiv lungsjukdom (KOL) innebär svårigheter med andningsflödet genom luftvägarna. Sjukdomen utvecklas smygande och lungkapaciteten avtar gradvis. Sjuksköterskan bör se över patientens egenvårdsförmåga och därefter anpassa information/utbildning och stöd. Syfte: Att belysa omvårdnadsåtgärder som sjuksköterskan kan ta till hjälp för att främja egenvård hos patienter med KOL. Metod: 15 artiklar från PubMed och Cinahl analyserades med innehållsanalys och låg till grund för litteraturstudien. Även manuell sökning gjordes. Resultat: Två kategorier framträdde tydligt i resultatet; information/utbildning och stöd. Sjuksköterskans arbete med att informera/utbilda patienter samt att ge individuellt stöd kunde underlätta egenvårdsförmågan hos personer med KOL. Diskussion: För att uppnå egenvård fanns vissa centrala begrepp som sjuksköterskan kan följa; att få patienten delaktig, att situations-och individanpassa och att ha en helhetssyn. Konklusion: Mer kunskap och träning i att informera/utbilda samt att ge stöd till personer med KOL behövdes för att deras behov skulle tillgodoses.</p>

<p>Att drabbas av KOL är något som påverkar vardagen på många sätt. Sjukdomen har ökat i omfattning och visar inga tecken på att minska. Det innebär att vårdpersonal alltmer kommer att möta dessa personer. Behandlingen är oftast inriktad mot de fysiska behoven utan att ta hänsyn till helheten. Syftet var att belysa dessa personers upplevelser av att leva med KOL för att kunna möta deras behov och ge det stöd de själva vill ha. Litteraturstudie valdes som metod och systematiska sökningar gjordes i databaserna Cinahl, Pubmed och PsycINFO. Resultatet bygger på 14 artiklar och visade att andningsproblemen var den dominerade upplevelsen som påverkade vardagen negativt. Andningsproblemen gjorde att personerna med KOL upplevde att de tappade orken, upplevde beroende, men även så småningom en acceptans över att leva med den kroniska sjukdomen. Det visade sig hur dessa upplevelser påverkade varandra och kunde bli som en ond cirkel. Det är därför viktigt att i fortsatt forskning undersöka hur vårdpersonalen kan stödja dessa personers egenvårdsstrategier där peer-support är en viktig del.</p>

Background: Air pollution is associated with negative health effects. Exposure to combustion-derived particulate matter (PM) air pollution has been related to increased incidence of cardiovascular and respiratory morbidity and mortality, specifically in susceptible populations. Ambient particles, with a diameter of less than 2.5 mm, have been suggested to be the strongest contributor to these health effects. Diesel exhaust (DE) is a major source of small combustion-derived PM air pollution world wide.  In healthy volunteers, exposure to DE, has been associated with airway inflammation and impaired vasomotor function and endogenous fibrinolysis. The aims of this thesis were to further elucidate the underlying mechanisms to the reported cardiovascular effects following exposure to DE, with specific focus on endothelin-1 (ET-1). Additionally, the vascular effects of the major gaseous component of DE, nitrogen dioxide (NO2), were assessed together with the impact of an exhaust particle trap to reduce the observed negative vascular effects after DE exposure. Methods: In all studies healthy, non-smoking male volunteers were included and exposed for one hour during intermittent exercise in a randomised double-blind crossover fashion. In studies I-III, subjects were exposed to DE at a particulate matter concentration of approximately 300 μg/m3 and filtered air, on two different occasions. In study V an additional exposure was employed, during which DE was filtered through an exhaust particle trap. In study IV subjects were exposed to nitrogen dioxide (NO2) at 4 ppm or filtered air. In study I, thrombus formation and platelet activation were assessed using the Badimon ex vivo perfusion chamber and flow cytometry. Study II comprised the determination of arterial stiffness including pulse wave analysis and velocity. In studies III-V, vascular assessment was performed using venous occlusion plethysmography. In studies IV and V, the vascular responses to intra-arterially infused endothelial-dependent and endothelial-independent vasodilatators were registered. In study III, vascular responses to intra-arterial infusion of Endothelin-1 (ET-1) and ET-1-receptor antagonists were assessed. Venous occlusion phlethysmography was in all cases performed 4-6 hours following exposures. Blood samples for markers of inflammation, coagulation and platelet activation were collected before and throughout the study periods in studies III and V. Results: Exposure to DE increased ex vivo thrombus formation and arterial stiffness, in terms of augmentation index. DE inhalation impaired vasomotor function and endogenous fibrinolysis. The exhaust particle trap reduced the particle concentration by 98% and abolished the effects on vasomotor function, endogenous fibrinolysis and ex vivo thrombus formation. Plasma concentrations of ET-1 and its precursor big-ET-1 were unchanged following exposure. Dual endothelial receptor antagonism caused similar vasodilatation after both exposures, although vasodilatation to the endothelin-A receptor alone was blunted after DE exposure. ET-1 infusion induced vasoconstriction only following DE exposure. Exposure to nitrogen dioxide did not affect vascular function. Conclusion: Inhalation of diesel exhaust in young healthy men impaired important and complementary aspects of vascular function in humans; regulation of vascular tone and endogenous fibrinolysis as well as increased ex vivo thrombus formation. The use of an exhaust particle trap significantly reduced particle emissions and abolished the DE-induced vascular and prothrombotic effects. The adverse vascular effects following DE exposure do not appear to be directly mediated through the endothelin system. Neither is NO2 suggested to be a major arbiter of the DE-induced cardiovascular responses. Arterial stiffness is a non-invasive and easily accessible method and could thus be employed to address vascular function in larger field studies. Taken together, this thesis has given further knowledge about the mechanisms underlying the DE-induced vascular effects.

It is well established that air pollution has detrimental effects on both human health as well as the environment. Exposure to ozone and particulate matter pollution, is associated with an increase in cardiopulmonary mortality and morbidity. Asthmatics, elderly and children have been indicated as especially sensitive groups. With a global increase in use of vehicles and industry, ambient air pollution represents a crucial health concern as well as a political, economical and environmental dilemma. Both ozone (O3) and diesel exhaust (DE) trigger oxidative stress and inflammation in the airways, causing symptoms such as wheezing, coughing and reduced lung function. The aim of this thesis was to further examine which pro-inflammatory signaling pathways that are initiated in the airways by ozone, as compared to diesel exhaust. Furthermore, to study the effects of these two ambient air pollutants in a sequential exposure, thus mimicking an urban profile. In order to investigate this in healthy as well as asthmatic subjects, walk-in exposure chambers were utilized and various airway compartments were studied by obtaining induced sputum, endobronchial biopsies, or airway lavage fluids. In asthmatic subjects, exposure to 0.2 ppm of O3 induced an increase in the cytokines IL 5, GM-CSF and ENA-78 in the bronchial epithelium six hours post-exposure. The healthy subjects, however, displayed no elevations of bronchial epithelial cytokine expression in response to the ozone exposure. The heightened levels of neutrophil chemoattractants and Th2 cytokines in the asthmatic airway epithelium may contribute to symptom exacerbations following air pollution exposure. When examining an earlier time point post O3 exposure (1½ hours), healthy subjects exhibited a suppression of IL-8 as well as of the transcription factors NFκB and c-jun in the bronchial epithelium, as opposed to after filtered air exposure. This inhibition of early signal transduction in the bronchial epithelium after O3 differs from the response detected after exposure to DE. Since both O3 and DE are associated with generating airway neutrophilia as well as causing direct oxidative damage, it raises the query of whether daily exposure to these two air pollutants creates a synergistic or additive effect. Induced sputum attained from healthy subjects exposed in sequence to 0.2 ppm of O3 five hours following DE at a PM concentration of 300 µg/m3, demonstrated significantly increased neutrophils, and elevated MPO levels, as compared to the sequential DE and filtered air exposure. O3 and DE interactions were further investigated by analyses of bronchoalveolar lavage and bronchial wash. It was demonstrated that pre-exposure to DE, as compared to filtered air, enhances the O3-induced airway inflammation, in terms of an increase in neutrophil and macrophage numbers in BW and higher EPX expression in BAL. In conclusion, this thesis has aspired to expand the knowledge of O3-induced inflammatory pathways in humans, observing a divergence to the previously described DE initiated responses. Moreover, a potentially adverse airway inflammation augmentation has been revealed after exposure to a relevant ambient combination of these air pollutants. This provides a foundation towards an understanding of the cumulative airway effects when exposed to a combination of ambient air pollutants and may have implications regarding future regulations of exposure limits.

The overall aim of this work was to examine the effects of depleted nutritional status on some aspects of Chronic Obstructive Pulmonary Disease (COPD). Morbidity. In paper І, we found that energy intake was lower than the calculated energy demand for all patients. A low body mass index (BMI) at inclusion and weight loss, during the one year follow-up period were independent risk factors for having a new exacerbation (p = 0.003 and 0.006, respectively). Mortality. Nineteen percent of the patients in paper ІІ, where underweight (BMI&lt;20). A significant positive correlation was found between BMI and FEV1, and this correlation remained significant after adjustment for age, sex and pack years (p&lt;0.0001). Being underweight was related to increased overall mortality and respiratory mortality but not to mortality of other causes, 19% of the patients had died within 2 years. The lowest mortality was found among the overweight patients (BMI 25-30 kg/m). Physical capacity and effect of training. In paper ІІІ we investigated baseline characteristics of patients that were starting physical training. We found that peak working capacity was positively related to BMI (r=0.35, p=0.02) and fat free mass index (FFMI) (r=0.49, p=0.004) and negatively related to S-Fibrinogen and serum C reactive protein (S-CRP). BMI and FFMI were significantly related to the 12 minutes walking distance when adjusted for body weight. Fifty to 76% of the variation in physical capacity was accounted for when age, gender, FEV1, FFMI and CRP were combined in a multiple regression model. In Paper ІV the median change in fat free mass (FFM), after 4 months of physical training was 0.5 kg. Old age, low FEV1 and high level of dyspnoea were independent negative predictors of FFM increase after the training period. In conclusion nutritional status is an important determinant of morbidity, mortality and physical capacity in COPD. Low FEV1 and high level of dyspnea are negative predictors for increased FFM after physical training.

Bakgrund: Kronisk obstruktiv lungsjukdom (KOL) innebär svårigheter med andningsflödet genom luftvägarna. Sjukdomen utvecklas smygande och lungkapaciteten avtar gradvis. Sjuksköterskan bör se över patientens egenvårdsförmåga och därefter anpassa information/utbildning och stöd. Syfte: Att belysa omvårdnadsåtgärder som sjuksköterskan kan ta till hjälp för att främja egenvård hos patienter med KOL. Metod: 15 artiklar från PubMed och Cinahl analyserades med innehållsanalys och låg till grund för litteraturstudien. Även manuell sökning gjordes. Resultat: Två kategorier framträdde tydligt i resultatet; information/utbildning och stöd. Sjuksköterskans arbete med att informera/utbilda patienter samt att ge individuellt stöd kunde underlätta egenvårdsförmågan hos personer med KOL. Diskussion: För att uppnå egenvård fanns vissa centrala begrepp som sjuksköterskan kan följa; att få patienten delaktig, att situations-och individanpassa och att ha en helhetssyn. Konklusion: Mer kunskap och träning i att informera/utbilda samt att ge stöd till personer med KOL behövdes för att deras behov skulle tillgodoses.

Att drabbas av KOL är något som påverkar vardagen på många sätt. Sjukdomen har ökat i omfattning och visar inga tecken på att minska. Det innebär att vårdpersonal alltmer kommer att möta dessa personer. Behandlingen är oftast inriktad mot de fysiska behoven utan att ta hänsyn till helheten. Syftet var att belysa dessa personers upplevelser av att leva med KOL för att kunna möta deras behov och ge det stöd de själva vill ha. Litteraturstudie valdes som metod och systematiska sökningar gjordes i databaserna Cinahl, Pubmed och PsycINFO. Resultatet bygger på 14 artiklar och visade att andningsproblemen var den dominerade upplevelsen som påverkade vardagen negativt. Andningsproblemen gjorde att personerna med KOL upplevde att de tappade orken, upplevde beroende, men även så småningom en acceptans över att leva med den kroniska sjukdomen. Det visade sig hur dessa upplevelser påverkade varandra och kunde bli som en ond cirkel. Det är därför viktigt att i fortsatt forskning undersöka hur vårdpersonalen kan stödja dessa personers egenvårdsstrategier där peer-support är en viktig del.