| 1. |
- Calder, Philip C, et al.
(författare)
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Early nutrition and immunity - progress and perspectives.
- 2006
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Ingår i: The British journal of nutrition. - 0007-1145. ; 96:4, s. 774-90
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Forskningsöversikt (refereegranskat)abstract
- The immune system exists to protect the host against pathogenic organisms and highly complex pathways of recognition, response, elimination and memory have evolved in order to fulfil this role. The immune system also acts to ensure tolerance to 'self', to food and other environmental components, and to commensal bacteria. A breakdown in the tolerogenic pathways can also lead to inflammatory diseases. The prevalence of inflammatory diseases, including atopic disorders, has increased over the last 60 years. The development of tolerance is the result of active immune mechanisms and both development and maintenance of tolerance are lifelong processes which start very early in life, even prenatally. Profound immunologic changes occur during pregnancy, involving a polarization of T helper (Th) cells towards a dominance of Th2 and regulatory T cell effector responses in both mother and fetus. This situation is important to maintain pregnancy through avoidance of the rejection of the immunologically incompatible fetus. During the third trimester of human pregnancy, fetal T cells are able to mount antigen-specific responses to environmental and food-derived antigens and antigen-specific T cells are detectable in cord blood in virtually all newborns indicating in utero sensitization. If the neonatal immune system is not able to down-regulate the pre-existing Th2 dominance effectively then an allergic phenotype may develop. Changes occur at, and soon after, birth in order that the immune system of the neonate becomes competent and functional and that the gut becomes colonized with bacteria. Exposure to bacteria during birth and from the mother's skin and the provision of immunologic factors in breast milk are amongst the key events that promote maturation of the infant's gut and gut-associated and systemic immune systems. The introduction of formula and of solid foods exposes the infant to novel food antigens and also affects the gut flora. Nutrition may be the source of antigens to which the immune system must become tolerant, provide factors, including nutrients, that themselves might modulate immune maturation and responses, and provide factors that influence intestinal flora, which in turn will affect antigen exposure, immune maturation and immune responses. Through these mechanisms it is possible that nutrition early in life might affect later immune competence, the ability to mount an appropriate immune response upon infection, the ability to develop a tolerogenic response to 'self' and to benign environmental antigens, and the development of immunologic disorders. A Workshop held in February 2006 considered recent findings in the areas of oral tolerance, routes of sensitization to allergens and factors affecting the development of atopic disease; factors influencing the maturation of dendritic cells and the development of regulatory T cells; the influence of gut microflora on immunity, allergic sensitization and infectious disease; the role of nutrition in preventing necrotizing enterocolitis in an animal model of preterm birth; and the role of PUFA of different classes in influencing immune responses and in shaping the development of atopic disease. This report summarizes the content of the lectures and the subsequent discussions.
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| 2. |
- Castro-Giner, Francesc, et al.
(författare)
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Traffic-related air pollution, oxidative stress genes, and asthma (ECHRS)
- 2009
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 117:12, s. 1919-1924
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Traffic-related air pollution is related with asthma, and this association may be modified by genetic factors. OBJECTIVES: We investigated the role of genetic polymorphisms potentially modifying the association between home outdoor levels of modeled nitrogen dioxide and asthma. METHODS: Adults from 13 cities of the second European Community Respiratory Health Survey (ECRHS II) were included (n = 2,920), for whom both DNA and outdoor NO(2) estimates were available. Home addresses were geocoded and linked to modeled outdoor NO(2) estimates, as a marker of local traffic-related pollution. We examined asthma prevalence and evaluated polymorphisms in genes involved in oxidative stress pathways [gluthatione S-transferases M1 (GSTM1), T1 (GSTT1), and P1 (GSTP1) and NAD(P)H:quinine oxidoreductase (NQO1)], inflammatory response [tumor necrosis factor alpha (TNFA)], immunologic response [Toll-like receptor 4 (TLR4)], and airway reactivity [adrenergic receptor beta2 (ADRB2)]. RESULTS: The association between modeled NO(2) and asthma prevalence was significant for carriers of the most common genotypes of NQO1 rs2917666 [odds ratio (OR) = 1.54; 95% confidence interval (CI), 1.10-2.24], TNFA rs2844484 (OR = 2.02; 95% CI, 1.30-3.27). For new-onset asthma, the effect of NO(2) was significant for the most common genotype of NQO1 rs2917666 (OR = 1.52; 95% CI, 1.09-2.16). A significant interaction was found between NQO1 rs2917666 and NO(2) for asthma prevalence (p = 0.02) and new-onset asthma (p = 0.04). CONCLUSIONS: Genetic polymorphisms in the NQO1 gene are related to asthma susceptibility among persons exposed to local traffic-related air pollution. This points to the importance of antioxidant pathways in the protection against the effects of air pollution on asthma.
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| 3. |
- Cerveri, Isa, et al.
(författare)
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Underestimation of airflow obstruction among young adults using FEV1/FVC<70% as a fixed cut-off : a longitudinal evaluation of clinical and functional outcomes
- 2008
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 63:12, s. 1040-1045
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of airflow obstruction is particularly important among young adults because they are more likely to benefit from intervention. Using the forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) (FEV1/FVC) <70% fixed ratio, airflow obstruction may be underdiagnosed. The lower limit of normal (LLN), which is statistically defined by the lower fifth percentile of a reference population, is physiologically appropriate but it still needs a clinical validation.Methods: To evaluate the characteristics and longitudinal outcomes of subjects misidentified as normal by the fixed ratio with respect to the LLN, 6249 participants (aged 20-44 years) in the European Community Respiratory Health Survey were examined and divided into three groups (absence of airflow obstruction by the LLN and the fixed ratio; presence of airflow obstruction only by the LLN; presence of airflow obstruction by the two criteria) for 1991-1993. LLN equations were obtained from normal non-smoking participants. A set of clinical and functional outcomes was evaluated in 1999-2002.Results: The misidentified subjects were 318 (5.1%); only 45.6% of the subjects with airflow obstruction by the LLN were also identified by the fixed cut-off. At baseline, FEV1 (107%, 97%, 85%) progressively decreased and bronchial hyperresponsiveness (slope 7.84, 6.32, 5.57) progressively increased across the three groups. During follow-up, misidentified subjects had a significantly higher risk of developing chronic obstructive pulmonary disease and a significantly higher use of health resources (medicines, emergency department visits/hospital admissions) because of breathing problems than subjects without airflow obstruction (p<0.001).Conclusions: Our findings show the importance of using statistically derived spirometric criteria to identify airflow obstruction.
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| 4. |
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| 5. |
- Chinn, Susan, et al.
(författare)
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Bronchial responsiveness in atopic adults increases with exposure to cat allergen
- 2007
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 176:1, s. 20-26
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: The association of asthma with sensitization and allergen exposure is known to be complex. There have been few studies of bronchial responsiveness in relation to both risk factors in adults. Objectives: To determine the relation of bronchial responsiveness to allergen exposure and IgE sensitization in a community study taking into account the major determinants of bronchial responsiveness in adulthood. Methods: Cross-sectional data were drawn from 1,884 participants in 20 centers in the European Community Respiratory Health Survey follow-up, which included measurement of house dust mite and cat allergen in mattress dust samples, and IgE sensitization to four allergens. Bronchial responsiveness to methacholine was expressed as a continuous variable, and analyzed by multiple regression. Measurements and Main Results: The trend toward greater bronchial responsiveness with increasing exposure to cat allergen was greater in those sensitized to any of the four allergens than those not sensitized (p = 0.001); there was no significant interaction between cat sensitization and Fel d 1 exposure. No trend was found with house dust mite allergen exposure. The difference in bronchial responsiveness between those exposed to the highest levels compared with the lowest was approximately –2.02 doubling doses of PD20 (95% confidence interval, –3.06 to –0.97), and nearly as great in those exposed to more moderate levels. Conclusions: Cat allergen exposure at moderate levels may be harmful to all atopic adults. The clinical implication is that it is insufficient to test patients with asthma for cat sensitization; all atopic individuals may benefit from reduced cat exposure.
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| 6. |
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| 7. |
- de Marco, Roberto, et al.
(författare)
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Incidence of chronic obstructive pulmonary disease in a cohort of young adults according to the presence of chronic cough and phlegm
- 2007
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 175:1, s. 32-39
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: The few prospective studies aimed at assessing the incidence of chronic obstructive pulmonary disease (COPD) in relation to the presence of chronic cough/phlegm have produced contrasting results. Objectives: To assess the incidence of COPD in a cohort of young adults and to test whether chronic cough/phlegm and dyspnea are independent predictors of COPD. Methods: An international cohort of 5,002 subjects without asthma (ages 20-44 yr) with normal lung function (FEV1/FVC ratio ≥ 70%) from 12 countries was followed from 1991-2002 in the frame of the European Community Respiratory Health Survey II. Incident cases of COPD were those who had an FEV 1/FVC ratio less than 70% at the end of the follow-up, but did not report having had a doctor diagnose asthma during the follow-up. Main Results: The incidence rate of COPD was 2.8 cases/1,000/yr (95% confidence interval [CI], 2.3-3.3). Chronic cough/phlegm was an independent and statistically significant predictor of COPD (incidence rate ratio [IRR], 1.85; 95% CI, 1.17-2.93) after adjusting for smoking habits and other potential confounders, whereas dyspnea was not associated with the disease (IRR = 0.98; 95% CI, 0.64-1.50). Subjects who reported chronic cough/phlegm both at baseline and at the follow-up had a nearly threefold-increased risk of developing COPD with respect to asymptomatic subjects (IRR = 2.88; 95% CI, 1.44-5.79). Conclusions: The incidence of COPD is substantial even in young adults. The presence of chronic cough/phlegm identifies a subgroup of subjects with a high risk of developing COPD, independently of smoking habits.
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| 8. |
- de Marco, Roberto, et al.
(författare)
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Long-term outcomes in mild/moderate chronic obstructive pulmonary disease in the European community respiratory health survey
- 2009
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 180:10, s. 956-963
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Little is known about the long-term outcomes of individuals with mild/moderate chronic obstructive pulmonary disease (COPD) according to spirometric criteria. OBJECTIVES: To test whether nonsmokers and asymptomatic subjects with a spirometric diagnosis of COPD have a steeper decrease in lung function and higher hospitalization rates than subjects without airway obstruction. METHODS: A total of 5,205 subjects without asthma (20-44 years of age) from the general population, with FEV(1) >or= 50% predicted at baseline, were followed for 9 years in the frame of an international cohort study. Percent decrease in FEV(1) (DeltaFEV(1)%) and the annual hospitalization rate for respiratory causes during the follow-up were assessed for each subject. MEASUREMENTS AND MAIN RESULTS: At baseline, 324 (6.2%) subjects had the prebronchodilator FEV(1)/FVC ratio less than the lower limit of normal (LLN-COPD), and 105 (2.0%) subjects had the same ratio less than 0.70 (modified GOLD-COPD). At follow-up, smokers with LLN-COPD (n = 205) had a greater mean DeltaFEV(1)% (1.7%; 95% confidence interval [CI], 0.8-2.7) and a higher hospitalization rate (rate ratio [RR], 2.52; 95% CI, 1.65-3.86) than normal subjects. Similarly, symptomatic subjects with LLN-COPD (n = 104) had DeltaFEV(1)% (2.0%; 95% CI, 0.8-3.3) and the hospitalization rate (RR, 4.18; 95% CI, 2.43-7.21) higher than the reference group. By contrast, nonsmokers and asymptomatic subjects with LLN-COPD had outcomes that were similar or even better than normal subjects. Among subjects with LLN-COPD, the association of symptoms with DeltaFEV(1)% varied according to smoking habits (P = 0.007); it was particularly strong in symptomatic smokers and disappeared in symptomatic nonsmokers. Similar results were found with the modified GOLD classification. CONCLUSIONS: In relatively young populations, COPD is associated with poor long-term outcomes in smokers and in symptomatic subjects only.
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| 9. |
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Depression - zwischen Lebensgefühl und Krankheit
- 2005. - 1
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Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- Momente von Depression stecken in den alltäglichen Lebensentwürfen und Beziehungsmustern ebenso wie in den Gestaltungen von Literatur, Film, Musik und bildender Kunst. Sie können als Anzeichen einer verschlechterten Stimmungslage des heutigen Menschen gelten, als pathologische Kehrseite der modernen Beschleunigungen, eines Zeitgeistes, der die inneren und äußeren Freiräume des Individuums derart bedroht, dass Kreativität, Entfaltung von Selbst und Identität im Extremfall zum Stillstand kommen. Oder sind Depressionen einfach Ausdruck von Stimmungsschwankungen, wie sie seit jeher im Seelenleben vorkommen? Dieser Band stellt die psychoanalytischen Facetten des Phänomens Depression vor, wie er sich ebenso mit der nichtpathologischen Seite beschäftigt.
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| 10. |
- Götschi, Thomas, et al.
(författare)
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Air pollution and lung function in the European Community Respiratory Health Survey.
- 2008
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Ingår i: International journal of epidemiology. - : Oxford University Press (OUP). - 1464-3685 .- 0300-5771. ; 37:6, s. 1349-58
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The association of long-term air pollution and lung function has not been studied across adult European multi-national populations before. The aim of this study was to determine the association between long-term urban background air pollution and lung function levels, as well as change in lung function among European adults. METHODS: Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and the ratio thereof (FEV1/FVC) were assessed at baseline and after 9 years of follow-up in adults from 21 European centres (followed-up sample 5610). Fine particles (PM(2.5)) were measured in 2000/2001 using central monitors. RESULTS: Despite sufficient statistical power no significant associations were found between city-specific annual mean PM(2.5) and average lung function levels. The findings also do not support an effect on change in lung function, albeit statistical power was insufficient to significantly detect such an association. CONCLUSIONS: The inability to refuse the null hypothesis may reflect (i) no effect of urban air pollution on lung function or (ii) inherent biases due to the study design. Examples of the latter are lack of individual-level air quality assignment, not quantified within-city contrasts in traffic-related pollution, or the heterogeneity of the studied populations and their urban environments. Future studies on long-term effects of air pollution on lung function could increase statistical power and reduce potential misclassification and confounding by characterizing exposure on the level of individuals, capturing contrasts due to local sources, in particular traffic.
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