| 1. |
- Allinson, James, et al.
(författare)
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Collating data from major European population studies - The CADSET (Chronic airway disease early stratification) clinical research collaboration
- 2020
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 56:suppl 64
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: European population cohorts continue to expand our understanding of chronic airways disease and inter-study collaboration may help address the inevitable limitations of study size, duration, era and geography. Towards this aim, CADSET has collated data from ten major general population European cohorts: Asklepios; Copenhagen City Heart Study; Copenhagen General Population Study; ECRHS; HUNT; LEAD; Lifelines, OLIN, Rotterdam Study and WSAS. We included males and females aged 20 to 95 years with baseline demographic and spirometry data.Results: Data from 262,829 individuals (44% male) from multiple European countries provided good coverage across all adult ages (Fig.1A). Recruitment occurred in every year from 1976 through 2020. 23% were current-smokers and 42% were never-smokers, a pattern varying with advancing age (Fig.1B). The prevalence of airflow limitation varied according to whether lower limit of normal (LLN) or <0.70 thresholds were applied, increasing with age if the latter was used (Fig.1C).Interpretation: These results fit with previous reports, however the size, geographical reach and span of recruitment provided by this collaboration provides a unique opportunity to explore chronic airways disease development. Together, we are now pursuing research questions previously beyond the scope of individual cohort studies.
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| 2. |
- Allinson, James P, et al.
(författare)
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Changes in lung function in European adults born between 1884 and 1996 and implications for the diagnosis of lung disease: a cross-sectional analysis of ten population-based studies.
- 2022
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Ingår i: The Lancet. Respiratory medicine. - : Elsevier. - 2213-2619 .- 2213-2600. ; 10:1, s. 83-94
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Tidskriftsartikel (refereegranskat)abstract
- During the past century, socioeconomic and scientific advances have resulted in changes in the health and physique of European populations. Accompanying improvements in lung function, if unrecognised, could result in the misclassification of lung function measurements and misdiagnosis of lung diseases. We therefore investigated changes in population lung function with birth year across the past century, accounting for increasing population height, and examined how such changes might influence the interpretation of lung function measurements.In our analyses of cross-sectional data from ten European population-based studies, we included individuals aged 20-94 years who were born between 1884 and 1996, regardless of previous respiratory diagnoses or symptoms. FEV1, forced vital capacity (FVC), height, weight, and smoking behaviour were measured between 1965 and 2016. We used meta-regression to investigate how FEV1 and FVC (adjusting for age, study, height, sex, smoking status, smoking pack-years, and weight) and the FEV1/FVC ratio (adjusting for age, study, sex, and smoking status) changed with birth year. Using estimates from these models, we graphically explored how mean lung function values would be expected to progressively deviate from predicted values. To substantiate our findings, we used linear regression to investigate how the FEV1 and FVC values predicted by 32 reference equations published between 1961 and 2015 changed with estimated birth year.Across the ten included studies, we included 243465 European participants (mean age 51·4 years, 95% CI 51·4-51·5) in our analysis, of whom 136275 (56·0%) were female and 107190 (44·0%) were male. After full adjustment, FEV1 increased by 4·8 mL/birth year (95% CI 2·6-7·0; p<0·0001) and FVC increased by 8·8 mL/birth year (5·7-12·0; p<0·0001). Birth year-related increases in the FEV1 and FVC values predicted by published reference equations corroborated these findings. This height-independent increase in FEV1 and FVC across the last century will have caused mean population values to progressively exceed previously predicted values. However, the population mean adjusted FEV1/FVC ratio decreased by 0·11 per 100 birth years (95% CI 0·09-0·14; p<0·0001).If current diagnostic criteria remain unchanged, the identified shifts in European values will allow the easier fulfilment of diagnostic criteria for lung diseases such as chronic obstructive pulmonary disease, but the systematic underestimation of lung disease severity.The European Respiratory Society, AstraZeneca, Chiesi Farmaceutici, GlaxoSmithKline, Menarini, and Sanofi-Genzyme.
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| 3. |
- Andersén, Heidi, et al.
(författare)
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Is there still a social gradient in respiratory symptoms? A population-based nordic EpiLung-study
- 2024
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Ingår i: Respiratory Medicine. - : Elsevier. - 0954-6111 .- 1532-3064. ; 223
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Tidskriftsartikel (refereegranskat)abstract
- Background: Respiratory symptoms are a common public health issue that can partly be attributed to preventable risk factors, such as tobacco smoking and occupational exposure, which are more common in individuals with lower socioeconomic status.Objective: Our aim was to evaluate the social gradient in respiratory symptoms in Nordic countries.Methods: This study included participants aged 30–65 years from five cross-sectional population-based questionnaire surveys in 2016 in Finland and Sweden (N = 25,423) and in 2017–2019 in Norway (N = 27,107). Occupational skill levels 1 and 2 (occupations requiring compulsory education) were combined and compared to skill levels 3 and 4 (occupations requiring upper secondary and tertiary education). Meta-analysis was conducted to obtain pooled age- and sex adjusted odds ratios (aORs) of associations between occupational skill and the respiratory symptoms including recurrent wheeze, dyspnoea, and productive cough.Results: In the meta-analysis, recurrent wheeze, dyspnoea, and productive cough showed a social gradient. The participants with occupational skill 1 and 2 had higher risk for recurrent wheeze (aOR 1.78, 95% CI 1.34–2.22) and dyspnoea (aOR 1.59, 95% CI 1.29–1.90) compared to occupational skill 3 and 4 in Sweden and Finland. Similarly increased risk was observed for combined assessment of dyspnoea and wheeze (aOR 1.05, 95% CI 1.03–1.07) in Norway. In a meta-analysis including all three countries, the aOR for productive cough was 1.31 95% CI 1.07–1.56.Conclusions: Occupations with lower, compared to higher, skill levels were associated with an increased risk of recurrent wheeze, dyspnoea, and productive cough.
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| 4. |
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| 5. |
- Austin, Thomas R., et al.
(författare)
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A plasma protein-based risk score to predict hip fractures
- 2024
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Ingår i: NATURE AGING. - 2662-8465.
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Tidskriftsartikel (refereegranskat)abstract
- As there are effective treatments to reduce hip fractures, identification of patients at high risk of hip fracture is important to inform efficient intervention strategies. To obtain a new tool for hip fracture prediction, we developed a protein-based risk score in the Cardiovascular Health Study using an aptamer-based proteomic platform. The proteomic risk score predicted incident hip fractures and improved hip fracture discrimination in two Tr & oslash;ndelag Health Study validation cohorts using the same aptamer-based platform. When transferred to an antibody-based proteomic platform in a UK Biobank validation cohort, the proteomic risk score was strongly associated with hip fractures (hazard ratio per s.d. increase, 1.64; 95% confidence interval 1.53-1.77). The proteomic risk score, but not available polygenic risk scores for fractures or bone mineral density, improved the C-index beyond the fracture risk assessment tool (FRAX), which integrates information from clinical risk factors (C-index, FRAX 0.735 versus FRAX + proteomic risk score 0.776). The developed proteomic risk score constitutes a new tool for stratifying patients according to hip fracture risk; however, its improvement in hip fracture discrimination is modest and its clinical utility beyond FRAX with information on femoral neck bone mineral density remains to be determined. The authors developed a proteomic risk score that improved the prediction of hip fractures in three validation cohorts analyzed by two different proteomic platforms. This risk score constitutes a new tool to stratify patients by hip fracture risk.
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| 6. |
- Austin, Thomas R, et al.
(författare)
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Large-scale circulating proteome association study (CPAS) meta-analysis identifies circulating proteins and pathways predicting incident hip fractures.
- 2024
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - 1523-4681. ; 39:2, s. 139-149
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Tidskriftsartikel (refereegranskat)abstract
- Hip fractures are associated with significant disability, high cost, and mortality. However, the exact biological mechanisms underlying susceptibility to hip fractures remain incompletely understood. In an exploratory search of the underlying biology as reflected through the circulating proteome, we performed a comprehensive Circulating Proteome Association Study (CPAS) meta-analysis for incident hip fractures. Analyses included 6430 subjects from two prospective cohort studies (Cardiovascular Health Study and Trøndelag Health Study) with circulating proteomics data (aptamer-based 5K SomaScan version 4.0 assay; 4979 aptamers). Associations between circulating protein levels and incident hip fractures were estimated for each cohort using age and sex-adjusted Cox regression models. Participants experienced 643 incident hip fractures. Compared with the individual studies, inverse-variance weighted meta-analyses yielded more statistically significant associations, identifying 23 aptamers associated with incident hip fractures (conservative Bonferroni correction 0.05/4979, P<1.0×10-5). The aptamers most strongly associated with hip fracture risk corresponded to two proteins of the growth hormone/insulin growth factor system (GHR and IGFBP2), as well as GDF15 and EGFR. High levels of several inflammation-related proteins (CD14, CXCL12, MMP12, ITIH3) were also associated with increased hip fracture risk. Ingenuity pathway analysis identified reduced LXR/RXR activation and increased acute phase response signaling to be overrepresented among those proteins associated with increased hip fracture risk. These analyses identified several circulating proteins and pathways consistently associated with incident hip fractures. These findings underscore the usefulness of the meta-analytic approach for comprehensive CPAS in a similar manner as has previously been observed for large-scale human genetic studies. Future studies should investigate the underlying biology of these potential novel drug targets.
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| 7. |
- Axelsson, Malin, et al.
(författare)
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Differences in diagnostic patterns of obstructive airway disease between areas and sex in Sweden and Finland : The Nordic EpiLung Study
- 2021
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Ingår i: Journal of Asthma. - : Taylor & Francis. - 0277-0903 .- 1532-4303. ; 58:9, s. 1196-1207
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the current prevalence of physician-diagnosed obstructive airway diseases by respiratory symptoms and by sex in Sweden and Finland. Method: In 2016, a postal questionnaire was answered by 34,072 randomly selected adults in four study areas: Västra Götaland and Norrbotten in Sweden, and Seinäjoki-Vaasa and Helsinki in Finland. Results: The prevalence of asthma symptoms was higher in Norrbotten (13.2%), Seinäjoki-Vaasa (14.8%) and Helsinki (14.4%) than in Västra Götaland (10.7%), and physician-diagnosed asthma was highest in Norrbotten (13.0%) and least in Västra Götaland (10.1%). Chronic productive cough was most common in the Finnish areas (7.7-8.2 % versus 6.3-6.7 %) while the prevalence of physician-diagnosed chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD) varied between 1.7-2.7% in the four areas. Among individuals with respiratory symptoms, the prevalence of asthma was most common in Norrbotten, while a diagnosis of COPD or CB was most common in Västra Götaland and Seinäjoki-Vaasa. More women than men with respiratory symptoms reported a diagnosis of asthma in Sweden and Seinäjoki-Vaasa but there were no sex differences in Helsinki. In Sweden, more women than men with symptoms of cough or phlegm reported a diagnosis of CB or COPD, while in Finland the opposite was found. Conclusion: The prevalence of respiratory symptoms and corresponding diagnoses varied between and within the countries. The proportion reporting a diagnosis of obstructive airway disease among individuals with respiratory symptoms varied, indicating differences in diagnostic patterns both between areas and by sex.
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| 8. |
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| 9. |
- Backman, Helena, et al.
(författare)
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Level of Education Modifies Asthma Mortality in Norway and Sweden. The Nordic EpiLung Study
- 2024
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Ingår i: JOURNAL OF ASTHMA AND ALLERGY. - : Dove Medical Press. - 1178-6965. ; 17, s. 209-218
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aim: The relationship between socioeconomic status (SES), asthma and mortality is complex and multifaceted, and it is not established if educational level modifies the association between asthma and mortality. The aim was to study the association between asthma and mortality in Sweden and Norway and to what extent educational level modifies this association. Participants and Methods: Within the Nordic EpiLung Study, >56,000 individuals aged 30-69 years participated in population -based surveys on asthma and associated risk factors in Sweden and Norway during 2005-2007. Data on educational level and 10-year all -cause mortality were linked by national authorities. The fraction of mortality risk attributable to asthma was calculated, and Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for mortality related to asthma, stratified by educational level. Results: In total, 5.5% of all deaths was attributed to asthma. When adjusted for potential confounders, the HR for mortality related to asthma was 1.71 (95% CI 1.52-1.93). Those with primary level of education had higher hazard of all -cause death related to asthma than those with tertiary level (HR 1.80, 95% CI 1.48-2.18, vs HR 1.39, 95% CI 0.99-1.95). Conclusion: Asthma was associated with an overall 71% increased all -cause mortality and 5.5% of deaths can be attributed to asthma. Educational levels modified the risk of mortality associated with asthma, with the highest risk among those with primary education.
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| 10. |
- Backman, Helena, 1979-
(författare)
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Lung function and prevalence trends in asthma and COPD
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Asthma and chronic obstructive pulmonary disease (COPD) are common obstructive airway diseases with a substantial burden in terms of morbidity, mortality and costs. Smoking is the single most important risk factor for COPD, and is associated with incident asthma. It is important to know if the prevalence of asthma and COPD is increasing or decreasing in the population in order to effectively allocate health care resources. The definitions of these diseases have varied over time which makes it difficult to measure changes in prevalence. The preferred method is to estimate the prevalence with the same procedures and definitions based on cross-sectional population samples with identical age distributions in the same geographical area at different time points. Measurements of lung function (spirometry) are required to diagnose COPD, and spirometry is used to evaluate disease severity and progress of both asthma and COPD, where observed values are compared to reference values. The most commonly used reference values in Sweden are published during the mid 1980s, and there are few evaluations of how appropriate they are today based on Swedish population samples. The aim of the thesis was to estimate trends in the prevalence of asthma and COPD in relation to smoking habits, and to evaluate and estimate reference values for spirometry.Methods: The project was based on population-based samples of adults from the Obstructive Lung Disease in Northern Sweden (OLIN) studies. Postal questionnaires were sent to large cohorts, recruited in 1992 (n=4851, 20-69 years), 1996 (n=7420, 20-74 years) and 2006 (n=6165, 20-69 years), respectively. The questionnaire included questions on respiratory symptoms and diseases, their comorbidities and several possible risk factors including smoking habits. Structured interviews and spirometry were performed in random samples of the responders to the 1992 and 2006 surveys, of which n=660 (in 1994) and n=623 (in 2009) were within identical age-spans (23-72 years). The trend in asthma prevalence was estimated by comparing the postal questionnaire surveys in 1996 and 2006, and the trend in COPD prevalence was estimated by comparing the samples participating in dynamic spirometry in 1994 and 2009, respectively. The prevalence of COPD was estimated based on two different definitions of COPD. Commonly used reference values for spirometry were evaluated based on randomly sampled healthy non-smokers defined in clinical examinations of participants in the 2006 postal questionnaire (n=501). The main focus of the evaluation was the global lung function initiative (GLI) reference values published in 2012, for which Z-scores and percent of predicted values were analysed. New sex-specific reference values for spirometry were estimated by linear regression, with age and height as predictors. These new OLIN reference values were also evaluated on a sample of healthy non-smokers identified in the population-based West Sweden Asthma Study.Results: Although the prevalence of smoking decreased from 27.4% to 19.1%, p<0.001, between 1996 and 2006, the prevalence of physician-diagnosed asthma increased from 9.4% to 11.6%, p<0.001. The prevalence of symptoms common in asthma such as recurrent wheeze did not change significantly between the surveys or tended to decrease, while bronchitis symptoms such as cough and sputum production decreased significantly. The evaluation of the GLI reference values showed that the predicted values were significantly lower compared to the observed values in Norrbotten, which makes the percent of predicted too high. This was especially true for FVC percent predicted with a mean of 106%. In general, the deviations were more pronounced among women. New OLIN reference values valid for the Norrbotten sample were modelled and showed a high external validity when applied on the sample from western Sweden. The prevalence of moderate to severe COPD decreased substantially over the 15-year period between 1994 and 2009, regardless of definition.Conclusions: In parallel with substantially decreased smoking habits in the population between 1996 and 2006, the prevalence of several airway symptoms decreased while the prevalence of physician-diagnosed asthma increased. These results suggest increased diagnostic activity for asthma, but may also suggest that the asthma prevalence has continued to increase. In contrast to asthma, the prevalence of COPD tended to decrease and moderate to severe COPD decreased substantially. The continuous decrease in smoking in Sweden during several decades prior to the study period is most likely contributing to these results. The evaluation of reference values showed that the GLI reference values were lower than the observed spirometric values in the population, especially for women, why the new up-to date reference values may be of importance for disease evaluation in epidemiology and in the health care as well.
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| 11. |
- Backman, Helena, et al.
(författare)
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Respiratory symptoms as risk factors for mortality – the Nordic EpiLung Study
- 2020
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 56:Suppl 64
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Little is known on associations between respiratory symptoms and mortality.Aim: To study whether respiratory symptoms are risk factors for all-cause, respiratory, cardiovascular (CV), and cancer mortality in Sweden and Norway.Methods: In 1995-1997, population samples (20-69y) were surveyed about respiratory symptoms, and n=7,104 (85.3% of invited, median age 45y) and n=54,240 (70.1%, 44y) participated within the OLIN Studies in Northern Sweden and the HUNT Study in Norway. Mortality was studied until December 31st 2015. Hazard ratios (HR) for associations between respiratory symptoms and mortality were estimated by Cox regression models adjusted for age, sex, educational level, and smoking habits.Results: The cumulative 20-year mortality was 14.5% in OLIN and 12.6% in HUNT. Dyspnea (mMRC grade≥2) (HR 1.9, 95%CI 1.6-2.2 in OLIN and 1.6, 1.5-1.7 in HUNT), chronic productive cough (1.5, 1.3-1.8 and 1.5, 1.3-1.6), and wheeze (1.3, 1.1-1.5 and 1.3, 1.2-1.4) were associated with increased risk of all-cause mortality. Women reported dyspnea and wheeze more frequently than men in both countries, but the association with mortality was similar in both sexes. Causes of death were studied in OLIN, where dyspnea associated with increased risk of respiratory (3.6, 2.1-6.1), CV (2.1, 1.6-2.7), and cancer (1.3, 1.0-1.8) mortality. Chronic productive cough was associated with increased risk of respiratory (2.4, 1.3-4.3) and cancer (1.6, 1.2-2.2) mortality, while wheeze was associated with increased risk of respiratory (3.5, 2.1-5.7) and CV (1.3, 1.0-1.6) mortality.Conclusions: Common respiratory symptoms were similarly associated with increased risk of mortality in adults in Sweden and Norway.
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| 12. |
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| 13. |
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| 14. |
- Ellingsen, Jens, 1979-
(författare)
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Chronic obstructive pulmonary disease: exacerbations and mortality : Prognostic value of biomarkers and comorbidities
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. COPD is associated with systemic inflammation, and comorbidities are common. A characteristic feature is acute exacerbations (AECOPDs), i.e., episodes of worsening symptoms. AECOPDs are associated with increased mortality.Aim: To find prognostic risk factors for COPD mortality and AECOPDs, focusing on comorbidities and inflammatory biomarkers.Methods: In Paper I, associations between comorbidities, pharmacological treatment, and mortality were analysed in a real-world cohort of almost 18,000 primary care COPD patients. Data from medical records and national registers were analysed in Cox proportional hazards regressions.Papers II–IV were based on the Tools Identifying Exacerbations (TIE) cohort study of 572 COPD patients recruited from primary and secondary care in three Swedish regions. Participants were invited to three yearly visits, including phlebotomy, spirometry, and health questionnaires.In Paper II, the ability of blood neutrophil-to-lymphocyte ratio (NLR) and eosinophils (B-Eos) to predict AECOPDs was analysed with mixed-effects logistic regressions.In Paper III, the ability of C-reactive protein (CRP), fibrinogen, blood leukocytes (B-Leu), and four blood cell indices to predict AECOPDs was analysed with ordinal logistic regressions.In Paper IV, an algorithm for clinical phenotyping previously developed to predict mortality was studied. The algorithm’s ability to predict AECOPDs and mortality was analysed with Cox proportional hazards regressions; additionally, the identified phenotypes were analysed concerning differences in blood-based inflammatory biomarkers.Results: Several comorbidities, including heart diseases, were associated with increased mortality risk. Some pharmacological treatments were associated with increased or decreased mortality risk (Paper I). NLR, B-Eos, CRP, fibrinogen, and B-Leu (Papers II–III) predicted AECOPDs after adjustment for confounders, whereas other blood cell indices were of limited value (Paper III). The clinical phenotyping algorithm predicted AECOPDs and mortality, and the phenotypes had different patterns of inflammatory biomarkers (Paper IV).Conclusions: Comorbidities, particularly heart diseases, are substantial risk factors for mortality in COPD and should be an integral part of management of COPD patients. NLR, B-Eos, CRP, fibrinogen, and B-Leu are independent predictors of AECOPDs and should be further investigated as parts of, e.g., risk prediction tools. A previously developed algorithm for clinical phenotyping predicts mortality and AECOPDs.
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| 15. |
- Fanidi, Anouar, et al.
(författare)
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Circulating Folate, Vitamin B6, and Methionine in Relation to Lung Cancer Risk in the Lung Cancer Cohort Consortium (LC3)
- 2018
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 110:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The extent to which these associations are present in other study populations is unknown.Methods: Within 20 prospective cohorts from the National Cancer Institute Cohort Consortium, a nested case-control study was designed including 5364 incident lung cancer case patients and 5364 control subjects who were individually matched to case patients by age, sex, cohort, and smoking status. Centralized biochemical analyses were performed to measure circulating concentrations of vitamin B6, folate, and methionine, as well as cotinine as an indicator of recent tobacco exposure. The association between these biomarkers and lung cancer risk was evaluated using conditional logistic regression models.Results: Participants with higher circulating concentrations of vitamin B6 and folate had a modestly decreased risk of lung cancer risk overall, the odds ratios when comparing the top and bottom fourths (OR 4vs1 ) being 0.88 (95% confidence interval [CI] = 0.78 to 1.00) and 0.86 (95% CI = 0.74 to 0.99), respectively. We found stronger associations among men (vitamin B6: OR 4vs1 = 0.74, 95% CI = 0.62 to 0.89; folate: OR 4vs1 = 0.75, 95% CI = 0.61 to 0.93) and ever smokers (vitamin B6: OR 4vs1 = 0.78, 95% CI = 0.67 to 0.91; folate: OR 4vs1 = 0.87, 95% CI = 0.73 to 1.03). We further noted that the association of folate was restricted to Europe/Australia and Asia, whereas no clear association was observed for the United States. Circulating concentrations of methionine were not associated with lung cancer risk overall or in important subgroups.Conclusions: Although confounding by tobacco exposure or reverse causation cannot be ruled out, these study results are compatible with a small decrease in lung cancer risk in ever smokers who avoid low concentrations of circulating folate and vitamin B6.
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| 16. |
- Fanidi, Anouar, et al.
(författare)
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Is high vitamin B12 status a cause of lung cancer?
- 2019
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 145:6, s. 1499-1503
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin B supplementation can have side effects for human health, including cancer risk. We aimed to elucidate the role of vitamin B12 in lung cancer etiology via direct measurements of pre‐diagnostic circulating vitamin B12 concentrations in a nested case–control study, complemented with a Mendelian randomization (MR) approach in an independent case–control sample. We used pre‐diagnostic biomarker data from 5183 case–control pairs nested within 20 prospective cohorts, and genetic data from 29,266 cases and 56,450 controls. Exposures included directly measured circulating vitamin B12 in pre‐diagnostic blood samples from the nested case–control study, and 8 single nucleotide polymorphisms associated with vitamin B12 concentrations in the MR study. Our main outcome of interest was increased risk for lung cancer, overall and by histological subtype, per increase in circulating vitamin B12 concentrations. We found circulating vitamin B12 to be positively associated with overall lung cancer risk in a dose response fashion (odds ratio for a doubling in B12 [ORlog2B12] = 1.15, 95% confidence interval (95%CI) = 1.06–1.25). The MR analysis based on 8 genetic variants also indicated that genetically determined higher vitamin B12 concentrations were positively associated with overall lung cancer risk (OR per 150 pmol/L standard deviation increase in B12 [ORSD] = 1.08, 95%CI = 1.00–1.16). Considering the consistency of these two independent and complementary analyses, these findings support the hypothesis that high vitamin B12 status increases the risk of lung cancer.
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| 17. |
- Feng, Xiaoshuang, et al.
(författare)
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Evaluation of pre-diagnostic blood protein measurements for predicting survival after lung cancer diagnosis
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
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Tidskriftsartikel (refereegranskat)abstract
- Background: To evaluate whether circulating proteins are associated with survival after lung cancer diagnosis, and whether they can improve prediction of prognosis.Methods: We measured up to 1159 proteins in blood samples from 708 participants in 6 cohorts. Samples were collected within 3 years prior to lung cancer diagnosis. We used Cox proportional hazards models to identify proteins associated with overall mortality after lung cancer diagnosis. To evaluate model performance, we used a round-robin approach in which models were fit in 5 cohorts and evaluated in the 6th cohort. Specifically, we fit a model including 5 proteins and clinical parameters and compared its performance with clinical parameters only.Findings: There were 86 proteins nominally associated with mortality (p < 0.05), but only CDCP1 remained statistically significant after accounting for multiple testing (hazard ratio per standard deviation: 1.19, 95% CI: 1.10–1.30, unadjusted p = 0.00004). The external C-index for the protein-based model was 0.63 (95% CI: 0.61–0.66), compared with 0.62 (95% CI: 0.59–0.64) for the model with clinical parameters only. Inclusion of proteins did not provide a statistically significant improvement in discrimination (C-index difference: 0.015, 95% CI: −0.003 to 0.035).Interpretation: Blood proteins measured within 3 years prior to lung cancer diagnosis were not strongly associated with lung cancer survival, nor did they importantly improve prediction of prognosis beyond clinical information.
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| 18. |
- Feng, Xiaoshuang, et al.
(författare)
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Lung cancer risk discrimination of prediagnostic proteomics measurements compared with existing prediction tools
- 2023
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 115:9, s. 1050-1059
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a commercially available autoantibody biomarker test.METHODS: We designed a case-control study nested in 6 prospective cohorts, including 624 lung cancer participants who donated blood samples at most 3 years prior to lung cancer diagnosis and 624 smoking-matched cancer free participants who were assayed for 302 proteins. We used 470 case-control pairs from 4 cohorts to select proteins and train a protein-based risk model. We subsequently used 154 case-control pairs from 2 cohorts to compare the risk-discriminatory performance of the protein-based model with that of the Early Cancer Detection Test (EarlyCDT)-Lung and the PLCOm2012 model using receiver operating characteristics analysis and by estimating models' sensitivity. All tests were 2-sided.RESULTS: The area under the curve for the protein-based risk model in the validation sample was 0.75 (95% confidence interval [CI] = 0.70 to 0.81) compared with 0.64 (95% CI = 0.57 to 0.70) for the PLCOm2012 model (Pdifference = .001). The EarlyCDT-Lung had a sensitivity of 14% (95% CI = 8.2% to 19%) and a specificity of 86% (95% CI = 81% to 92%) for incident lung cancer. At the same specificity of 86%, the sensitivity for the protein-based risk model was estimated at 49% (95% CI = 41% to 57%) and 30% (95% CI = 23% to 37%) for the PLCOm2012 model.CONCLUSION: Circulating proteins showed promise in predicting incident lung cancer and outperformed a standard risk prediction model and the commercialized EarlyCDT-Lung.
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| 19. |
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| 20. |
- Grahnemo, Louise, et al.
(författare)
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Identification of three bacterial species associated with increased appendicular lean mass : the HUNT study.
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Appendicular lean mass (ALM) associates with mobility and bone mineral density (BMD). While associations between gut microbiota composition and ALM have been reported, previous studies rely on relatively small sample sizes. Here, we determine the associations between prevalent gut microbes and ALM in large discovery and replication cohorts with information on relevant confounders within the population-based Norwegian HUNT cohort (n = 5196, including women and men). We show that the presence of three bacterial species - Coprococcus comes, Dorea longicatena, and Eubacterium ventriosum - are reproducibly associated with higher ALM. When combined into an anabolic species count, participants with all three anabolic species have 0.80 kg higher ALM than those without any. In an exploratory analysis, the anabolic species count is positively associated with femoral neck and total hip BMD. We conclude that the anabolic species count may be used as a marker of ALM and BMD. The therapeutic potential of these anabolic species to prevent sarcopenia and osteoporosis needs to be determined.
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| 21. |
- Guida, Florence, et al.
(författare)
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The blood metabolome of incident kidney cancer: A case-control study nested within the MetKid consortium
- 2021
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Ingår i: PLoS Medicine. - : Public Library of Science (PLOS). - 1549-1277 .- 1549-1676. ; 18:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Excess bodyweight and related metabolic perturbations have been implicated in kidney cancer aetiology, but the specific molecular mechanisms underlying these relationships are poorly understood. In this study, we sought to identify circulating metabolites that predispose kidney cancer and to evaluate the extent to which they are influenced by body mass index (BMI).Methods and findings: We assessed the association between circulating levels of 1,416 metabolites and incident kidney cancer using pre-diagnostic blood samples from up to 1,305 kidney cancer case–control pairs from 5 prospective cohort studies. Cases were diagnosed on average 8 years after blood collection. We found 25 metabolites robustly associated with kidney cancer risk. In particular, 14 glycerophospholipids (GPLs) were inversely associated with risk, including 8 phosphatidylcholines (PCs) and 2 plasmalogens. The PC with the strongest association was PC ae C34:3 with an odds ratio (OR) for 1 standard deviation (SD) increment of 0.75 (95% confidence interval [CI]: 0.68 to 0.83, p = 2.6 × 10−8). In contrast, 4 amino acids, including glutamate (OR for 1 SD = 1.39, 95% CI: 1.20 to 1.60, p = 1.6 × 10−5), were positively associated with risk. Adjusting for BMI partly attenuated the risk association for some—but not all—metabolites, whereas other known risk factors of kidney cancer, such as smoking and alcohol consumption, had minimal impact on the observed associations. A mendelian randomisation (MR) analysis of the influence of BMI on the blood metabolome highlighted that some metabolites associated with kidney cancer risk are influenced by BMI. Specifically, elevated BMI appeared to decrease levels of several GPLs that were also found inversely associated with kidney cancer risk (e.g., −0.17 SD change [ßBMI] in 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2) levels per SD change in BMI, p = 3.4 × 10−5). BMI was also associated with increased levels of glutamate (ßBMI: 0.12, p = 1.5 × 10−3). While our results were robust across the participating studies, they were limited to study participants of European descent, and it will, therefore, be important to evaluate if our findings can be generalised to populations with different genetic backgrounds.Conclusions: This study suggests a potentially important role of the blood metabolome in kidney cancer aetiology by highlighting a wide range of metabolites associated with the risk of developing kidney cancer and the extent to which changes in levels of these metabolites are driven by BMI - the principal modifiable risk factor of kidney cancer.
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| 22. |
- Gustafsson, Stefan, et al.
(författare)
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Markers of imminent myocardial infarction
- 2024
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Ingår i: Nature Cardiovascular Research. - : Springer Nature. - 2731-0590.
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Tidskriftsartikel (refereegranskat)abstract
- Myocardial infarction is a leading cause of death globally but is notoriously difficult to predict. We aimed to identify biomarkers of an imminent first myocardial infarction and design relevant prediction models. Here, we constructed a new case–cohort consortium of 2,018 persons without prior cardiovascular disease from six European cohorts, among whom 420 developed a first myocardial infarction within 6 months after the baseline blood draw. We analyzed 817 proteins and 1,025 metabolites in biobanked blood and 16 clinical variables. Forty-eight proteins, 43 metabolites, age, sex and systolic blood pressure were associated with the risk of an imminent first myocardial infarction. Brain natriuretic peptide was most consistently associated with the risk of imminent myocardial infarction. Using clinically readily available variables, we devised a prediction model for an imminent first myocardial infarction for clinical use in the general population, with good discriminatory performance and potential for motivating primary prevention efforts.
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| 23. |
- Huang, Joyce Y., et al.
(författare)
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Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3)
- 2020
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 146:9, s. 2394-2405
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Tidskriftsartikel (refereegranskat)abstract
- Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all p(trend) < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.
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| 24. |
- Ilmarinen, Pinja, et al.
(författare)
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Level of education and asthma control in adult-onset asthma
- 2022
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Ingår i: The Journal of asthma : official journal of the Association for the Care of Asthma. - : Informa UK Limited. - 1532-4303 .- 0277-0903. ; 59:4, s. 840-849
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Education in itself and as a proxy for socioeconomic status, may influence asthma control, but remains poorly studied in adult-onset asthma. Our aim was to study the association between the level of education and asthma control in adult-onset asthma. Methods: Subjects with current asthma with onset >15years were examined within the Obstructive Lung Disease in Northern Sweden study (OLIN, n=593), Seinäjoki Adult Asthma Study (SAAS, n=200), and West Sweden Asthma Study (WSAS, n=301) in 2009-2014 in a cross-sectional setting. Educational level was classified as primary, secondary and tertiary. Uncontrolled asthma was defined as Asthma Control Test (ACT) score ≤19. Altogether, 896 subjects with complete data on ACT and education were included (OLIN n=511, SAAS n=200 and WSAS n=185). Results: In each cohort and in pooled data of all cohorts, median ACT score was lower among those with primary education than in those with secondary and tertiary education. Uncontrolled asthma was most common among those with primary education, especially among daily ICS users (42.6% primary, 28.6% secondary and 24.2% tertiary; p=0.001). In adjusted analysis, primary education was associated with uncontrolled asthma in daily ICS users (OR 1.92, 95%CI 1.15-3.20). When stratified by atopy, the association between primary education and uncontrolled asthma was seen in non-atopic (OR 3.42, 95%CI 1.30-8.96) but not in atopic subjects. Conclusions: In high-income Nordic countries, lower educational level was a risk factor for uncontrolled asthma in subjects with adult-onset asthma. Educational level should be considered in the management of adult-onset asthma.
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| 25. |
- Jalasto, Juuso, et al.
(författare)
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Mortality associated with occupational exposure in Helsinki, Finland : a 24-year follow-up
- 2023
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Ingår i: Journal of Occupational and Environmental Medicine. - : Wolters Kluwer. - 1076-2752 .- 1536-5948. ; 65:1, s. 22-28
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Our objective was to study mortality related to different obstructive lung diseases, occupational exposure, and their potential joint effect in a large, randomized population-based cohort. Methods We divided the participants based on the answers to asthma and chronic obstructive pulmonary disease (COPD) diagnoses and occupational exposure and used a combined effects model and compared the results to no asthma or COPD with no occupational exposure. Results High exposure had a hazards ratio (HR) of 1.34 (1.11-1.62) and asthma and COPD coexistence of 1.58 (1.10-2.27). The combined effects of intermediate exposure and coexistence had an HR of 2.20 (1.18-4.09), high exposure with coexistence of 1.94 (1.10-3.42) for overall mortality, and sub-HR for respiratory-related mortality of 3.21 (1.87-5.50). Conclusions High occupational exposure increased overall but not respiratory-related mortality hazards, while coexisting asthma and COPD overall and respiratory-related hazards of mortality.
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