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- Backman, Helena, et al.
(author)
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Decreased COPD prevalence in Sweden after decades of decrease in smoking
- 2020
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In: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 21
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Journal article (peer-reviewed)abstract
- BackgroundCOPD has increased in prevalence worldwide over several decades until the first decade after the millennium shift. Evidence from a few recent population studies indicate that the prevalence may be levelling or even decreasing in some areas in Europe. Since the 1970s, a substantial and ongoing decrease in smoking prevalence has been observed in several European countries including Sweden. The aim of the current study was to estimate the prevalence, characteristics and risk factors for COPD in the Swedish general population. A further aim was to estimate the prevalence trend of COPD in Northern Sweden from 1994 to 2009.MethodsTwo large random population samples were invited to spirometry with bronchodilator testing and structured interviews in 2009–2012, one in south-western and one in northern Sweden, n = 1839 participants in total. The results from northern Sweden were compared to a study performed 15 years earlier in the same area and age-span. The diagnosis of COPD required both chronic airway obstruction (CAO) and the presence of respiratory symptoms, in line with the GOLD documents since 2017. CAO was defined as post-bronchodilator FEV1/FVC < 0.70, with sensitivity analyses based on the FEV1/FVC < lower limit of normal (LLN) criterion.ResultsBased on the fixed ratio definition, the prevalence of COPD was 7.0% (men 8.3%; women 5.8%) in 2009–2012. The prevalence of moderate to severe (GOLD ≥ 2) COPD was 3.5%. The LLN based results were about 30% lower. Smoking, occupational exposures, and older age were risk factors for COPD, whereof smoking was the most dominating risk factor. In northern Sweden the prevalence of COPD, particularly moderate to severe COPD, decreased significantly from 1994 to 2009, and the decrease followed a decrease in smoking.ConclusionsThe prevalence of COPD has decreased in Sweden, and the prevalence of moderate to severe COPD was particularly low. The decrease follows a major decrease in smoking prevalence over several decades, but smoking remained the dominating risk factor for COPD.
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- Bao, Erik L, et al.
(author)
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Inherited myeloproliferative neoplasm risk affects haematopoietic stem cells
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 586:7831, s. 769-775
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Journal article (peer-reviewed)abstract
- Myeloproliferative neoplasms (MPNs) are blood cancers that are characterized by the excessive production of mature myeloid cells and arise from the acquisition of somatic driver mutations in haematopoietic stem cells (HSCs). Epidemiological studies indicate a substantial heritable component of MPNs that is among the highest known for cancers1. However, only a limited number of genetic risk loci have been identified, and the underlying biological mechanisms that lead to the acquisition of MPNs remain unclear. Here, by conducting a large-scale genome-wide association study (3,797 cases and 1,152,977 controls), we identify 17 MPN risk loci (P < 5.0 × 10-8), 7 of which have not been previously reported. We find that there is a shared genetic architecture between MPN risk and several haematopoietic traits from distinct lineages; that there is an enrichment for MPN risk variants within accessible chromatin of HSCs; and that increased MPN risk is associated with longer telomere length in leukocytes and other clonal haematopoietic states-collectively suggesting that MPN risk is associated with the function and self-renewal of HSCs. We use gene mapping to identify modulators of HSC biology linked to MPN risk, and show through targeted variant-to-function assays that CHEK2 and GFI1B have roles in altering the function of HSCs to confer disease risk. Overall, our results reveal a previously unappreciated mechanism for inherited MPN risk through the modulation of HSC function.
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- Elbagir, Sahwa, 1983-
(author)
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Autoimmunity in Africa: Comparing Systemic Lupus Erythematosus and Anti-phospholipid Antibodies in Sudan and Sweden
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Systemic Lupus Erythematosus (SLE) is a chronic immune complex (IC)-mediated disease with variable prevalence worldwide, reported to be more common in Africans, Hispanics and Asians than in Caucasian populations. Expression of autoantibodies might vary between different ethnic populations due to environmental and genetic factors. Antiphospholipid antibodies (aPL) react with several antigenic targets of negatively charged phospholipids and/or associated plasma proteins. In this thesis we have studied the immunological and clinical characteristics of SLE in patients from Sudan and Sweden using an identical methodology. We have also investigated the occurrence of aPL during healthy pregnancies in both countries.Sudanese patients with SLE were younger, had shorter disease duration and suffered from more organ damage compared to Swedish patients. Neurological involvement, predominantly in young patients, was the main contributor to organ damage among the Sudanese patients. When comparing anti-nuclear antibody (ANA) specificities in IC between Sudanese and Swedish patients, different results from ANA detected in serum was observed. While serum ANA levels were mainly higher in Swedish SLE patients, levels of most ANA specificities in IC, particularly anti-chromatin specificities, were increased in Sudanese patients. In both cohorts, ANA in IC associated with more active SLE. Sudanese SLE patients had a higher prevalence of IgA aPL using common assay cut-off points. However, aPL levels among controls were also higher in Sudan, and when cut-offs were adjusted based on national controls the difference in prevalence between the patient groups was no longer evident. A more recently defined test measuring antibody against the phosphatidylserine/prothrombin complex was the best aPL predictor of thrombosis in Swedish SLE patients, independent of cardiovascular risk factors and antiphospholipid antibody syndrome criteria tests. Levels of IgA aPL, particularly anti-β2 glycoprotein I, were higher in normal pregnancies of healthy women from Sudan. This was not observed in Swedish pregnancies, and it was not due to reactivity against domain 1 of the β2 glycoprotein I molecule.Levels of autoantibodies differed both for patients and healthy individuals from Sudan and Sweden, and the occurrence of antibodies among patients depended on the cut-offs used. Adjustments to national cut-offs revealed more associations between autoantibody occurrence and clinical manifestations in Sudan. We recommend that the evaluation of autoantibody prevalence and clinical significance in autoimmune diseases in populations of African origin should rely on cut-offs based on controls from the same population, both in research and clinical contexts.
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- Wennstig, Anna-Karin, 1973-, et al.
(author)
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Risk of coronary stenosis after adjuvant radiotherapy for breast cancer
- 2022
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In: Strahlentherapie und Onkologie (Print). - : Springer Berlin/Heidelberg. - 0179-7158 .- 1439-099X. ; 198, s. 630-638
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Journal article (peer-reviewed)abstract
- Purpose: Adjuvant radiotherapy (RT) for breast cancer is associated with an increased risk of ischemic heart disease. We examined the risk of coronary artery stenosis in a large cohort of women with breast cancer receiving adjuvant RT.Methods: A cohort of women diagnosed with breast cancer between 1992 and 2012 in three Swedish health care regions (n = 57,066) were linked to the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) to identify women receiving RT who subsequently underwent a percutaneous coronary intervention (PCI) due to coronary stenosis. Cox regression analyses were performed to examine risk of a coronary intervention and competing risk analyses were performed to calculate cumulative incidence.Results: A total of 649 women with left-sided breast cancer and 494 women with right-sided breast cancer underwent a PCI. Women who received left-sided RT had a significantly higher risk of a PCI in the left anterior descending artery (LAD) compared to women who received right-sided RT, hazard ratio (HR) 1.44 (95% confidence interval [CI] 1.21–1.77, p < 0.001). For the proximal, mid, and distal LAD, the HRs were 1.60 (95% CI 1.22–2.10), 1.38 (95% CI 1.07–1.78), and 2.43 (95% CI 1.33–4.41), respectively. The cumulative incidence of coronary events at 25 years from breast cancer diagnosis were 7.0% in women receiving left-sided RT and 4.4% in women receiving right-sided RT.Conclusion: Implementing and further developing techniques that lower cardiac doses is important in order to reduce the risk of long-term side effects of adjuvant RT for breast cancer.
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