| 1. |
- Bjerg, Anders, 1982, et al.
(författare)
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Higher Risk of Wheeze in Female than Male Smokers. Results from the Swedish GA(2)LEN Study
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Women who smoke have higher risk of lung function impairment, COPD and lung cancer than smoking men. An influence of sex hormones has been demonstrated, but the mechanisms are unclear and the associations often subject to confounding. This was a study of wheeze in relation to smoking and sex with adjustment for important confounders. Methods In 2008 the Global Allergy and Asthma European Network (GA2LEN) questionnaire was mailed to 45.000 Swedes (age 16–75 years), and 26.851 (60%) participated. “Any wheeze”: any wheeze during the last 12 months. “Asthmatic wheeze”: wheeze with breathlessness apart from colds. Results Any wheeze and asthmatic wheeze was reported by 17.3% and 7.1% of women, vs. 15.8% and 6.1% of men (both p<0.001). Although smoking prevalence was similar in both sexes, men had greater cumulative exposure, 16.2 pack-years vs. 12.8 in women (p<0.001). Most other exposures and characteristics associated with wheeze were significantly overrepresented in men. Adjusted for these potential confounders and pack-years, current smoking was a stronger risk factor for any wheeze in women aged <53 years, adjusted odds ratio (aOR) 1.85 (1.56–2.19) vs. 1.60 (1.30–1.96) in men. Cumulative smoke exposure and current smoking each interacted significantly with female sex, aOR 1.02 per pack-year (p<0.01) and aOR 1.28 (p = 0.04) respectively. Female compared to male current smokers also had greater risk of asthmatic wheeze, aOR 1.53 vs. 1.03, interaction aOR 1.52 (p = 0.02). These interactions were not seen in age ≥53 years. Discussion In addition to the increased risk of COPD and lung cancer female, compared to male, smokers are at greater risk of significant wheezing symptoms in younger age. This became clearer after adjustment for important confounders including cumulative smoke exposure. Estrogen has previously been shown to increase the bioactivation of several compounds in tobacco smoke, which may enhance smoke-induced airway inflammation in fertile women.
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| 2. |
- Heikkilä, Katriina, et al.
(författare)
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Job strain and COPD exacerbations: an individual-participant meta-analysis
- 2014
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 44:1, s. 247-251
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Tidskriftsartikel (refereegranskat)abstract
- To the Editor:Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and disability worldwide (1). The clinical course of COPD is characterised by exacerbations, which can be minor and manageable at home or in primary care, or severe, leading to hospitalisation or even death. Known causes of exacerbations include tobacco smoke, air pollution, dusts and fumes, and respiratory infections (1, 2). One less well understood risk factor is stress, which could plausibly lead to COPD exacerbations as it can trigger inflammation (3, 4) and is associated with increased smoking (5), which are both implicated in COPD pathology (2). Work is an important source of stress in the age groups in which COPD is typically diagnosed (1, 6). However, we are not aware of previous investigations of work-related stress and the risk of COPD exacerbations.In this study, we examined the associations between job strain (the most widely studied conceptualisation of work-related stress) and severe COPD exacerbations using individual-level data from 10 prospective cohort studies from the Individual Participant Data Meta-analysis in Working Populations (IPD-Work) Consortium (7). Job strain is defined as a combination of high demands (excessive amounts of work) and low control (having little influence on what tasks to.
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| 3. |
- Bråbäck, Lennart, et al.
(författare)
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Confounding with familial determinants affects the association between mode of delivery and childhood asthma medication : a national cohort study
- 2013
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Ingår i: Allergy, Asthma & Clinical Immunology. - : BioMed Central. - 1710-1484 .- 1710-1492. ; 9:1, s. 14-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mode of delivery may affect the risk of asthma but the findings have not been consistent and factors shared by siblings may confound the associations in previous studies. METHODS: The association between mode of delivery and dispensed inhaled corticosteroid (ICS) (a marker of asthma) was examined in a register based national cohort (n=199 837). A cohort analysis of all first born children aged 2-5 and 6-9 years was performed. An age-matched sibling-pair analysis was also performed to account for shared genetic and environmental risk factors. RESULTS: Analyses of first-borns demonstrated that elective caesarean section was associated with an increased risk of dispensed ICS in both 2-5 (adjusted odds ratio (aOR)=1.19, 95% confidence interval (CI) 1.09-1.29) and 6-9 (aOR=1.21, 1.09-1.34) age groups. In the sibling-pair analysis, the increased risk associated with elective caesarean section was confirmed in 2-5 year olds (aOR=1.22, 1.05-1.43) but not in 6-9 year olds (aOR=1.06, 0.78-1.44). Emergency caesarean section and vacuum extraction had some association with dispensed ICS in the analyses of first-borns but these associations were not confirmed in the sibling-pair analyses. CONCLUSIONS: Confounding by familial factors affects the association between mode of delivery and dispensed ICS. Despite this confounding, there was some evidence that elective caesarean section contributed to a modestly increased risk of dispensed ICS but only up to five years of age.
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| 4. |
- Forsberg, Anna, et al.
(författare)
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Pre- and post-natal Lactobacillus reuteri supplementation decreases allergen responsiveness in infancy
- 2013
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Ingår i: Clinical and Experimental Allergy. - : Wiley-Blackwell. - 0954-7894 .- 1365-2222. ; 43:4, s. 434-442
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundWe have previously shown that Lactobacillus reuteri supplementation from pregnancy week 36 and to the infant through the first year of life decreased the prevalence of IgE-associated eczema at 2 years. The underlying immunological mechanisms are unknown, however.ObjectiveTo investigate the immunomodulatory effect of probiotic supplementation on allergen- and mitogen-induced immune responses in children until 2 years of age.MethodsBlood mononuclear cells were collected at birth, 6, 12 and 24 months from 61 children (29 probiotic and 32 placebo treated) and cultured with ovalbumin, birch and cat extract and Phytohaemagglutinin (PHA). Cytokine and chemokine secretion was determined using an in-house multiplexed Luminex assay and ELISA. Real-time PCR was performed to investigate the Ebi3, Foxp3, GATA-3 and T-bet mRNA expression.ResultsProbiotic treatment was associated with low cat-induced Th2-like responses at 6 months (IL-5, P = 0.01, and IL-13, P = 0.009), with a similar trend for IL-5 at 12 months (P = 0.09). Cat-induced IFN-γ responses were also lower after probiotic than after placebo treatment at 24 months (P = 0.007), with similar findings for the anti-inflammatory IL-10 at birth (P = 0.001) and at 12 months (P = 0.009). At 24 months, Th2-associated CCL22 levels were lower in the probiotic than in the placebo group after birch stimulation (P = 0.02), with a similar trend after ovalbumin stimulation (P = 0.07). Lower CCL22 levels were recorded at 12 and 24 months (P = 0.03 and P = 0.01) after PHA stimulation.Conclusion and Clinical RelevanceLactobacillus reuteri supplementation decreases allergen responsiveness and may enhance immunoregulatory capacity during infancy. L. reuteri supplementation from week 36 and during the first year of life significantly decreases IgE-associated eczema and lowers allergen and mitogen responsiveness.
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| 5. |
- Barman, Malin, 1983, et al.
(författare)
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High Levels of Both n-3 and n-6 Long-Chain Polyunsaturated Fatty Acids in Cord Serum Phospholipids Predict Allergy Development
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Background Long-chain polyunsaturated fatty acids (LCPUFAs) reduce T-cell activation and dampen inflammation. They might thereby counteract the neonatal immune activation and hamper normal tolerance development to harmless environmental antigens. We investigated whether fatty acid composition of cord serum phospholipids affects allergy development up to age 13 years. Methods From a population-based birth-cohort born in 1996/7 and followed until 13 years of age (n = 794), we selected cases with atopic eczema (n = 37) or respiratory allergy (n = 44), as well as non-allergic non-sensitized controls (n = 48) based on diagnosis at 13 years of age. Cord and maternal sera obtained at delivery from cases and controls were analysed for proportions of saturated, monounsaturated and polyunsaturated fatty acids among serum phospholipids. Results The cord serum phospholipids from subject who later developed either respiratory allergy or atopic eczema had significantly higher proportions of 5/8 LCPUFA species, as well as total n-3 LCPUFA, total n-6 LCPUFA and total LCPUFA compared to cord serum phospholipids from controls who did not develop allergy (P<0.001 for all comparisons). Conversely, individuals later developing allergy had lower proportion of the monounsaturated fatty acid 18:1n-9 as well as total MUFA (p<0.001) among cord serum phospholipids. The risk of respiratory allergy at age 13 increased linearly with the proportion of n-3 LCPUFA (Ptrend<0.001), n-6 LCPUFA (Ptrend = 0.001), and total LCPUFA (Ptrend<0.001) and decreased linearly with the proportions of total MUFA (Ptrend = 0.025) in cord serum phospholipids. Furthermore, Kaplan-Meier estimates of allergy development demonstrated that total LCPUFA proportion in cord serum phospholipids was significantly associated with respiratory allergy (P = 0.008) and sensitization (P = 0.002), after control for sex and parental allergy. Conclusion A high proportion of long-chain PUFAs among cord serum phospholipids may predispose to allergy development. The mechanism is unknown, but may involve dampening of the physiologic immune activation in infancy needed for proper maturation of the infant's immune system.
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| 6. |
- Lowe, Adrian J, et al.
(författare)
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Impact of Maternal Obesity on Inhaled Corticosteroid Use in Childhood : A Registry Based Analysis of First Born Children and a Sibling Pair Analysis
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIt has been proposed that maternal obesity during pregnancy may increase the risk that the child develops allergic disease and asthma, although the mechanisms underpinning this relationship are currently unclear. We sought to assess if this association may be due to confounding by genetic or environmental risk factors that are common to maternal obesity and childhood asthma, using a sibling pair analysis.MethodsThe study population comprised a Swedish national cohort of term children born between 1992 and 2008 to native Swedish parents. Maternal body mass index (BMI) was measured at 8-10 weeks gestation. Unconditional logistic regression models were used to determine if maternal obesity was associated with increased risk of inhaled corticosteroid (ICS) in 431,718 first-born children, while adjusting for potential confounders. An age-matched discordant sib-pair analysis was performed, taking into account shared genetic and environmental risk factors.ResultsMaternal over-weight and obesity were associated with increased risk that the child would require ICS (for BMI >= 35 kg/m(2), aOR = 1.30, 95% CI = 1.10-1.52 compared with normal weight mothers) in children aged 6-12 years. Similar effects were seen in younger children, but in children aged 13-16 years, maternal obesity (BMI >= 30) was related to increased risk of ICS use in girls (aOR = 1.28, 95% CI = 1.07-1.53) but not boys (OR = 1.05, 95% CI = 0.87-1.26). The sib-pair analysis, which included 2,034 sib-pairs older than six years who were discordant for both ICS use and maternal BMI category, failed to find any evidence that increasing maternal weight was related to increased risk of ICS use.ConclusionMaternal obesity is associated with increased risk of childhood ICS use up to approximately 12 years of age, but only in girls after this age. These effects could not be confirmed in a sib pair analysis, suggesting either limited statistical power, or the effects of maternal BMI may be due to shared genetic or environmental risk factors.
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| 7. |
- Svensson, Sara L, et al.
(författare)
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Midkine and Pleiotrophin have bactericidal properties : preserved antibacterial activity in a family of Heparin-binding growth factors during evolution
- 2010
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 285:21, s. 16105-16115
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Tidskriftsartikel (refereegranskat)abstract
- Antibacterial peptides of the innate immune system combat pathogenic microbes, but often have additional roles in promoting inflammation and as growth factors during tissue repair. Midkine (MK) and pleiotrophin (PTN) are the only two members of a family of heparin-binding growth factors. They show restricted expression during embryogenesis and are up-regulated in neoplasia. In addition, MK shows constitutive and inflammation-dependent expression in some non-transformed tissues of the adult. In the present study, we show that both MK and PTN display strong antibacterial activity, present at physiological salt concentrations. Electron microscopy of bacteria and experiments using artificial lipid bilayers suggest that MK and PTN exert their antibacterial action via a membrane disruption mechanism. The predicted structure of PTN, employing the previously solved MK structure as a template, indicates that both molecules consist of two domains, each containing three antiparallel beta-sheets. The antibacterial activity was mapped to the unordered C-terminal tails of both molecules and the last beta-sheets of the N-terminals. Analysis of the highly conserved MK and PTN orthologues from the amphibian Xenopus laevis and the fish Danio rerio suggests that they also harbor antibacterial activity in the corresponding domains. In support of an evolutionary conserved function it was found that the more distant orthologue, insect Miple2 from Drosophila melanogaster, also displays strong antibacterial activity. Taken together, the findings suggest that MK and PTN, in addition to their earlier described activities, may have previously unrealized important roles as innate antibiotics.
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| 8. |
- Kondori, Nahid, 1967, et al.
(författare)
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High recovery rate of Exophiala dermatitidis in the airways of cystic fibrosis patients is associated with pancreatic insufficiency.
- 2011
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Ingår i: Journal of clinical microbiology. - 1098-660X. ; Mar (49):3, s. 1004-9
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Tidskriftsartikel (refereegranskat)abstract
- The black pigmented fungus, Exophiala dermatitidis is considered to be a harmless colonizer of the airways of cystic fibrosis (CF) patients. The aim of this study was to establish the recovery rate of E. dermatitidis in respiratory specimens of CF patients, transplant recipients and subjects with other respiratory disorders in Sweden. Secondly, we wished to determine if particular clinical traits were associated with E. dermatitidis colonization of the airways, and the antifungal susceptibility profiles of Exophiala strains. Sputum and bronchoalveolar lavage samples (n=492) derived from 275 patients were investigated. E. dermatitidis was isolated in respiratory specimens of 19% (18/97) of the CF patients but in none of the other patient categories. All isolates were recovered after 6-25 days of incubation on erythritol-chloramphenicol (ECA) medium. Morphological and genetic analyses confirmed species identity. Pancreatic insufficiency was positively associated with the presence of E. dermatitidis in sputum samples (P= 0.0198). Antifungal susceptibility tests demonstrated that voriconazole and posaconazole had the lowest MICs against E. dermatitidis. To conclude, E. dermatitidis is a frequent colonizer of the respiratory tract of CF patients in Sweden, and appears to be associated with more advanced disease. Whether E. dermatitidis is pathogenic or not remains to be elucidated.
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| 9. |
- Blodörn, Krister, et al.
(författare)
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Vaccine Safety and Efficacy Evaluation of a Recombinant Bovine Respiratory Syncytial Virus (BRSV) with Deletion of the SH Gene and Subunit Vaccines Based On Recombinant Human RSV Proteins: N-nanorings, P and M2-1, in Calves with Maternal Antibodies
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9, s. 1-17
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Tidskriftsartikel (refereegranskat)abstract
- The development of safe and effective vaccines against both bovine and human respiratory syncytial viruses (BRSV, HRSV) to be used in the presence of RSV-specific maternally-derived antibodies (MDA) remains a high priority in human and veterinary medicine. Herein, we present safety and efficacy results from a virulent BRSV challenge of calves with MDA, which were immunized with one of three vaccine candidates that allow serological differentiation of infected from vaccinated animals (DIVA): an SH gene-deleted recombinant BRSV (Delta SHrBRSV), and two subunit (SU) formulations based on HRSV-P, -M2- 1, and -N recombinant proteins displaying BRSV-F and -G epitopes, adjuvanted by either oil emulsion (Montanide ISA71(VG), SUMont) or immunostimulating complex matrices (AbISCO-300, SUAbis). Whereas all control animals developed severe respiratory disease and shed high levels of virus following BRSV challenge, Delta SHrBRSV-immunized calves demonstrated almost complete clinical and virological protection five weeks after a single intranasal vaccination. Although mucosal vaccination with DSHrBRSV failed to induce a detectable immunological response, there was a rapid and strong anamnestic mucosal BRSV-specific IgA, virus neutralizing antibody and local T cell response following challenge with virulent BRSV. Calves immunized twice intramuscularly, three weeks apart with SUMont were also well protected two weeks after boost. The protection was not as pronounced as that in Delta SHrBRSV-immunized animals, but superior to those immunized twice subcutaneously three weeks apart with SUAbis. Antibody responses induced by the subunit vaccines were non-neutralizing and not directed against BRSV F or G proteins. When formulated as SUMont but not as SUAbis, the HRSV N, P and M2-1 proteins induced strong systemic cross-protective cell-mediated immune responses detectable already after priming. Delta SHrBRSV and SUMont are two promising DIVA-compatible vaccines, apparently inducing protection by different immune responses that were influenced by vaccine-composition, immunization route and regimen.
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| 10. |
- Sundblad, B. M., et al.
(författare)
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Chronic obstructive pulmonary disease (COPD) during the two last years of life - A retrospective study of decedents
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Little is known about the management of patients suffering from chronic obstructive pulmonary disease (COPD) during the last years of life. The aim of the study was to describe how management of COPD is performed in Sweden during the last two years of life. Methods: From the nationwide Cause of Death register all individuals with COPD as the underlying cause of death during two years were identified in one sparsely and one densely populated area of Sweden. Data were collected from medical records using a pre-defined protocol, especially developed for this purpose. Results: Of 822 individuals with COPD as underlying cause of death, medical records from 729 were available. The COPD diagnosis was based on lung function measurements in approximately half of the patients and median age at COPD diagnosis was 74 years (range 34-95). Women died at younger age, median 78 years (range 52-96) than did men (80 years (51-99)). The median survival time from diagnosis to death was 6 years in men and women in both areas. Among women and men 8.3% and 4.3% were never smokers, respectively. The structure of COPD management differed between the two areas, with utilization of physiotherapists, dieticians and working therapists being more used in the northern area, likely because of differences in accessibility to care institutions. Conclusions: In Sweden COPD is mostly diagnosed late in life and often not verified by lung function measurements. Opposite to the general population, women with COPD die at a lower age than men. © 2013 Sundblad et al.
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