| 21. |
- Lassmann-Klee, Paul, et al.
(författare)
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Differences of FENO in adult general populations of Nordic regions
- 2019
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 54:Suppl. 63
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Tidskriftsartikel (övrigt vetenskapligt)abstract
- Background: Eventual differences of expiratory nitric oxide (FENO) levels in general populations of Nordic countries may reflect differences in eosinophilic inflammation at population level.Aim: To study the differences in FENO of Nordic regions and their epidemiological associations.Methods: From 1997 to 2003 we measured FENO (ppb) and conducted skin prick-tests for a random sample of adults (n=1498), aged 20-60 years from Finland (Helsinki), Sweden (Stockholm and Örebro) and Estonia (Narva and Saaremaa). We compared differences between regions by estimating odds ratios (OR) and 95% confidence intervals (CIs) for high FENO (>25 ppb) using logistic regression adjusted for gender, smoking and allergy. Finally, we estimated crude ORs and 95% CIs for high FENO and for asthma, rhinitis, current asthma symptoms and asthma medication.Results: The mean and standard deviation (SD) for FENO was 19(14) in Finland, 18(12) in Sweden and 16(15) in Estonia (p<0.001). Estonia had a lower mean FENO than other countries, with no differences between Finland and Sweden. Compared to Helsinki, the adjusted OR (95%CI) for high FENO was 0.42(0.21-0.81) in Stockholm, 0.65(0.43-0.98) in Örebro, 0.53(0.32-0.84) in Narva and 0.45(0.28-0.71) in Saaremaa. In Estonia, high FENO was associated with asthma, allergy, rhinitis, current asthma, and asthma medication; in Finland with rhinitis and use of short acting β-agonist; in Sweden with asthma and asthma medication. Smoking was associated with low FENO. Mean FENO in asthmatics was 24(19) in Finland, 20(12) in Sweden, and 43(49) in Estonia (p=0.07).Conclusions: We observed a higher mean FENO in Finland and Sweden compared to Estonia, and found no overall differences of FENO levels in asthmatics.
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| 22. |
- Midttun, Øivind, et al.
(författare)
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A cross-sectional study of inflammatory markers as determinants of circulating kynurenines in the Lung Cancer Cohort Consortium
- 2023
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Circulating concentrations of metabolites (collectively called kynurenines) in the kynurenine pathway of tryptophan metabolism increase during inflammation, particularly in response to interferon-gamma (IFN-γ). Neopterin and the kynurenine/tryptophan ratio (KTR) are IFN-γ induced inflammatory markers, and together with C-reactive protein (CRP) and kynurenines they are associated with various diseases, but comprehensive data on the strength of associations of inflammatory markers with circulating concentrations of kynurenines are lacking. We measured circulating concentrations of neopterin, CRP, tryptophan and seven kynurenines in 5314 controls from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). The associations of neopterin, KTR and CRP with kynurenines were investigated using regression models. In mixed models, one standard deviation (SD) higher KTR was associated with a 0.46 SD higher quinolinic acid (QA), and 0.31 SD higher 3-hydroxykynurenine (HK). One SD higher neopterin was associated with 0.48, 0.44, 0.36 and 0.28 SD higher KTR, QA, kynurenine and HK, respectively. KTR and neopterin respectively explained 24.1% and 16.7% of the variation in QA, and 11.4% and 7.5% of HK. CRP was only weakly associated with kynurenines in regression models. In summary, QA was the metabolite that was most strongly associated with the inflammatory markers. In general, the inflammatory markers were most strongly related to metabolites located along the tryptophan-NAD axis, which may support suggestions of increased production of NAD from tryptophan during inflammation.
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| 23. |
- Midttun, Øivind, et al.
(författare)
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Circulating concentrations of biomarkers and metabolites related to Vitamin status, one-carbon and the kynurenine pathways in US, Nordic, Asian, and Australian populations
- 2017
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Ingår i: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 105:6, s. 1314-1326
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Tidskriftsartikel (refereegranskat)abstract
- Background: Circulating concentrations of biomarkers that are related to Vitamin status vary by factors such as diet, fortification, and supplement use. Published biomarker concentrations have also been influenced by the variation across laboratories, which complicates a comparison of results from different studies. Objective: We robustly and comprehensively assessed differences in biomarkers that are related to Vitamin status across geographic regions. Design: The trial was a cross-sectional study in which we investigated 38 biomarkers that are related to Vitamin status and one-carbon and tryptophan metabolism in serum and plasma from 5314 healthy control subjects representing 20 cohorts recruited from the United States, Nordic countries, Asia, and Australia, participating in the Lung Cancer Cohort Consortium. All samples were analyzed in a centralized laboratory. Results: Circulating concentrations of riboflavin, pyridoxal 5≤-phosphate, folate, Vitamin B-12, all-trans retinol, 25-hydroxyVitamin D, and a-tocopherol as well as combined Vitamin scores that were based on these nutrients showed that the general B-Vitamin concentration was highest in the United States and that the B Vitamins and lipid soluble Vitamins were low in Asians. Conversely, circulating concentrations of metabolites that are inversely related to B Vitamins involved in the one-carbon and kynurenine pathways were high in Asians. The high B-Vitamin concentration in the United States appears to be driven mainly by multiVitamin-supplement users. Conclusions: The observed differences likely reflect the variation in intake of Vitamins and, in particular, the widespread multiVitamin-supplement use in the United States. The results provide valuable information about the differences in biomarkerconcentrations in populations across continents. Am J Clin Nutr 2017;105:1314-26.
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| 24. |
- Muller, David C., et al.
(författare)
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Circulating high sensitivity C reactive protein concentrations and risk of lung cancer : Nested case-control study within Lung Cancer Cohort Consortium
- 2019
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Ingår i: BMJ (Online). - : BMJ Publishing Group. - 1756-1833 .- 0959-8138. ; 364
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To conduct a comprehensive analysis of prospectively measured circulating high sensitivity C reactive protein (hsCRP) concentration and risk of lung cancer overall, by smoking status (never, former, and current smokers), and histological sub-type. Design Nested case-control study. setting 20 population based cohort studies in Asia, Europe, Australia, and the United States. ParticiPants 5299 patients with incident lung cancer, with individually incidence density matched controls. exPOsure Circulating hsCRP concentrations in prediagnostic serum or plasma samples. Main OutcOMe Measure Incident lung cancer diagnosis. results A positive association between circulating hsCRP concentration and the risk of lung cancer for current (odds ratio associated with a doubling in hsCRP concentration 1.09, 95% confidence interval 1.05 to 1.13) and former smokers (1.09, 1.04 to 1.14) was observed, but not for never smokers (P<0.01 for interaction). This association was strong and consistent across all histological subtypes, except for adenocarcinoma, which was not strongly associated with hsCRP concentration regardless of smoking status (odds ratio for adenocarcinoma overall 0.97, 95% confidence interval 0.94 to 1.01). The association between circulating hsCRP concentration and the risk of lung cancer was strongest in the first two years of follow-up for former and current smokers. Including hsCRP concentration in a risk model, in addition to smoking based variables, did not improve risk discrimination overall, but slightly improved discrimination for cancers diagnosed in the first two years of follow-up. cOnclusiOns Former and current smokers with higher circulating hsCRP concentrations had a higher risk of lung cancer overall. Circulating hsCRP concentration was not associated with the risk of lung adenocarcinoma. Circulating hsCRP concentration could be a prediagnostic marker of lung cancer rather than a causal risk factor.
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| 25. |
- Nethander, Maria, 1980, et al.
(författare)
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Assessment of the genetic and clinical determinants of hip fracture risk: Genome-wide association and Mendelian randomization study.
- 2022
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Ingår i: Cell reports. Medicine. - : Elsevier BV. - 2666-3791. ; 3:10
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Tidskriftsartikel (refereegranskat)abstract
- Hip fracture is the clinically most important fracture, but the genetic architecture of hip fracture is unclear. Here, we perform a large-scale hip fracture genome-wide association study meta-analysis and Mendelian randomization study using five cohorts from European biobanks. The results show that five genetic signals associate with hip fractures. Among these, one signal associates with falls, but not with bone mineral density (BMD), while four signals are in loci known to be involved in bone biology. Mendelian randomization analyses demonstrate a strong causal effect of decreased femoral neck BMD and moderate causal effects of Alzheimer's disease and having ever smoked regularly on risk of hip fractures. The substantial causal effect of decreased femoral neck BMD on hip fractures in both young and old subjects and in both men and women supports the use of change in femoral neck BMD as a surrogate outcome for hip fractures in clinical trials.
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| 26. |
- Pinnock, Hilary, et al.
(författare)
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The International Primary Care Respiratory Group (IPCRG) Research Needs Statement 2010
- 2010
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Ingår i: Primary Care Respiratory Journal. - : Springer Science and Business Media LLC. - 1471-4418 .- 1475-1534. ; 19:Suppl 1, s. S1-S20
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Respiratory diseases are a public health issue throughout the world, with high prevalence and morbidity. This Research Needs Statement from the International Primary Care Respiratory Group (IPCRG) aims to highlight unanswered questions on the management of respiratory diseases that are of importance to practising primary care clinicians. METHODS: An informal but inclusive consultation process was instigated in 2009. Draft statements in asthma, rhinitis, COPD, tobacco dependence, and respiratory infections were circulated widely to IPCRG members, other recognised experts, and representatives from a range of economic and healthcare backgrounds. An iterative process was used to generate, prioritise and refine research questions in each section. RESULTS: Two overarching themes emerged. Firstly, there is a real need for research to be undertaken within primary care, which recruits patients representative of primary care populations, evaluates interventions realistically delivered within primary care, and draws conclusions that will be meaningful to professionals working within primary care. Secondly, international and national guidelines exist, but there is little evidence on the best strategies for implementing recommendations. Disease-specific research questions focus on effective and cost-effective ways to prevent disease, confirm the diagnosis, assess control, manage treatment, and empower selfmanagement. Practical questions about how to deliver this comprehensive agenda in diverse primary care settings are highlighted. CONCLUSIONS: We hope that this Research Needs Statement will be used by clinicians and patients campaigning for answers to relevant questions, by researchers seeking funding to provide answers to these questions, and by funding bodies to enable them to prioritise research agendas.
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| 27. |
- Robbins, Hilary A., et al.
(författare)
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Design and methodological considerations for biomarker discovery and validation in the Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Program
- 2023
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Ingår i: Annals of Epidemiology. - : Elsevier. - 1047-2797 .- 1873-2585. ; 77, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- The Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) program is an NCI-funded initiative with an objective to develop tools to optimize low-dose CT (LDCT) lung cancer screening. Here, we describe the rationale and design for the Risk Biomarker and Nodule Malignancy projects within INTEGRAL. The overarching goal of these projects is to systematically investigate circulating protein markers to include on a panel for use (i) pre-LDCT, to identify people likely to benefit from screening, and (ii) post-LDCT, to differentiate benign versus malignant nodules. To identify informative proteins, the Risk Biomarker project measured 1161 proteins in a nested-case control study within 2 prospective cohorts (n = 252 lung cancer cases and 252 controls) and replicated associations for a subset of proteins in 4 cohorts (n = 479 cases and 479 controls). Eligible participants had a current or former history of smoking and cases were diagnosed up to 3 years following blood draw. The Nodule Malignancy project measured 1078 proteins among participants with a heavy smoking history within four LDCT screening studies (n = 425 cases diagnosed up to 5 years following blood draw, 430 benign-nodule controls, and 398 nodule-free controls). The INTEGRAL panel will enable absolute quantification of 21 proteins. We will evaluate its performance in the Risk Biomarker project using a case-cohort study including 14 cohorts (n = 1696 cases and 2926 subcohort representatives), and in the Nodule Malignancy project within five LDCT screening studies (n = 675 cases, 680 benign-nodule controls, and 648 nodule-free controls). Future progress to advance lung cancer early detection biomarkers will require carefully designed validation, translational, and comparative studies.
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| 28. |
- Spjuth, Ola, 1977-, et al.
(författare)
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Harmonising and linking biomedical and clinical data across disparate data archives to enable integrative cross-biobank research
- 2016
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 24:4, s. 521-528
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Tidskriftsartikel (refereegranskat)abstract
- A wealth of biospecimen samples are stored in modern globally distributed biobanks. Biomedical researchers worldwide need to be able to combine the available resources to improve the power of large-scale studies. A prerequisite for this effort is to be able to search and access phenotypic, clinical and other information about samples that are currently stored at biobanks in an integrated manner. However, privacy issues together with heterogeneous information systems and the lack of agreed-upon vocabularies have made specimen searching across multiple biobanks extremely challenging. We describe three case studies where we have linked samples and sample descriptions in order to facilitate global searching of available samples for research. The use cases include the ENGAGE (European Network for Genetic and Genomic Epidemiology) consortium comprising at least 39 cohorts, the SUMMIT (surrogate markers for micro- and macro-vascular hard endpoints for innovative diabetes tools) consortium and a pilot for data integration between a Swedish clinical health registry and a biobank. We used the Sample avAILability (SAIL) method for data linking: first, created harmonised variables and then annotated and made searchable information on the number of specimens available in individual biobanks for various phenotypic categories. By operating on this categorised availability data we sidestep many obstacles related to privacy that arise when handling real values and show that harmonised and annotated records about data availability across disparate biomedical archives provide a key methodological advance in pre-analysis exchange of information between biobanks, that is, during the project planning phase.
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| 29. |
- Theofylaktopoulou, Despoina, et al.
(författare)
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Impaired functional vitamin B6 status is associated with increased risk of lung cancer
- 2018
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Ingår i: International Journal of Cancer. - : John Wiley & Sons Inc.. - 0020-7136 .- 1097-0215. ; 142:12, s. 2425-2434
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Tidskriftsartikel (refereegranskat)abstract
- Circulating vitamin B6 levels have been found to be inversely associated with lung cancer. Most studies have focused on the B6 form pyridoxal 5′-phosphate (PLP), a direct biomarker influenced by inflammation and other factors. Using a functional B6 marker allows further investigation of the potential role of vitamin B6 status in the pathogenesis of lung cancer. We prospectively evaluated the association of the functional marker of vitamin B6 status, the 3-hydroxykynurenine:xanthurenic acid (HK:XA) ratio, with risk of lung cancer in a nested case–control study consisting of 5,364 matched case–control pairs from the Lung Cancer Cohort Consortium (LC3). We used conditional logistic regression to evaluate the association between HK:XA and lung cancer, and random effect models to combine results from different cohorts and regions. High levels of HK:XA, indicating impaired functional B6 status, were associated with an increased risk of lung cancer, the odds ratio comparing the fourth and the first quartiles (OR4th vs. 1st) was 1.25 (95% confidence interval, 1.10–1.41). Stratified analyses indicated that this association was primarily driven by cases diagnosed with squamous cell carcinoma. Notably, the risk associated with HK:XA was approximately 50% higher in groups with a high relative frequency of squamous cell carcinoma, i.e., men, former and current smokers. This risk of squamous cell carcinoma was present in both men and women regardless of smoking status.
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| 30. |
- Tollefsen, Elin, et al.
(författare)
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Adolescents with wheeze have increased risk of additional health problems. The Young-HUNT study, Norway
- 2007
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Ingår i: Preventive Medicine. - : Elsevier. - 1096-0260 .- 0091-7435. ; 44:2, s. 178-182
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To explore the hypothesis of an association between current wheeze and other health problems in adolescence and to investigate any sex differences. METHODS: N=8817 adolescents aged 13-19 years completed a self-administered questionnaire including questions on health and lifestyle in Norway (1995-1997). RESULTS: All subjective health problems were significantly more prevalent in current wheezers compared to non-wheezers (frequent headache: girls 18% vs. 9%, boys 8% vs. 3%; frequent neck and shoulder pain: girls 10% vs. 5%, boys 6% vs. 2%; frequent joint and muscle pain: girls 6% vs. 2%, boys 6% vs. 2%; and frequent abdominal pain: girls 10% vs. 3%, boys 3% vs.1%). In both sexes, adjusted for covariates, current wheezers had statistically significant increased risk of reporting frequent headache (girls OR=2.0, boys OR=2.9), frequent neck and shoulder pain (girls OR=1.9, boys OR=3.3), frequent joint and muscle pain (girls OR=2.7, boys OR=3.5) and frequent abdominal pain (girls OR=2.7, boys OR=2.0). CONCLUSIONS: Current adolescent wheezers reported more additional health problems compared to non-wheezers. Even if girls reported more symptoms in general, the associations were stronger in boys. The findings are important for the clinical approach to teenage wheezers and should increase doctors' awareness of coexistence of other health complaints in these patients.
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