| 1. |
- Alhamdow, Ayman, et al.
(författare)
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Low-level exposure to polycyclic aromatic hydrocarbons is associated with reduced lung function among Swedish young adults
- 2021
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 197
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Tidskriftsartikel (refereegranskat)abstract
- Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been linked to adverse pulmonary effects. However, the impact of low-level environmental PAH exposure on lung function in early adulthood remains uncertain. Objectives: To evaluate the associations between urinary PAH metabolites and lung function parameters in young adults. Methods: Urinary metabolites of pyrene, phenanthrene, and fluorene were analysed in 1000 young adults from Sweden (age 22–25 years) using LC-MS/MS. Lung function and eosinophilic airway inflammation were measured by spirometry and exhaled nitric oxide fraction (FeNO), respectively. Linear regression analysis was used to evaluate associations between PAH metabolites and the outcomes. Results: Median urinary concentrations of 1-OH-pyrene, ∑OH-phenanthrene, and ∑OH-fluorene were 0.066, 0.36, 0.22 μg/L, respectively. We found inverse associations of ∑OH-phenanthrene and ∑OH-fluorene with FEV1 and FVC, as well as between 1-OH-pyrene and FEV1/FVC ratio (adjusted P < 0.05; all participants). An increase of 1% in ∑OH-fluorene was associated with a decrease of 73 mL in FEV1 and 59 mL in FVC. In addition, ∑OH-phenanthrene concentrations were, in a dose-response manner, inversely associated with FEV1 (B from −109 to −48 compared with the lowest quartile of ∑OH-phenanthrene; p trend 0.004) and FVC (B from −159 to −102 compared with lowest quartile; p-trend <0.001). Similar dose-response associations were also observed between ∑OH-fluorene and FEV1 and FVC, as well as between 1-OH-pyrene and FEV1/FVC (p-trend <0.05). There was no association between PAH exposure and FeNO, nor was there an interaction with smoking, sex, or asthma. Conclusion: Low-level PAH exposure was, in a dose-response manner, associated with reduced lung function in young adults. Our findings have public health implications due to i) the widespread occurrence of PAHs in the environment and ii) the clinical relevance of lung function in predicting all-cause and cardiovascular disease mortality.
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| 2. |
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| 3. |
- Johansson, Åsa, et al.
(författare)
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Precision medicine in complex diseases - : Molecular subgrouping for improved prediction and treatment stratification
- 2023
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 1365-2796 .- 0954-6820. ; 294:4, s. 378-396
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Forskningsöversikt (refereegranskat)abstract
- Complex diseases are caused by a combination of genetic, lifestyle, and environmental factors and comprise common noncommunicable diseases, including allergies, cardiovascular disease, and psychiatric and metabolic disorders. More than 25% of Europeans suffer from a complex disease, and together these diseases account for 70% of all deaths. The use of genomic, molecular, or imaging data to develop accurate diagnostic tools for treatment recommendations and preventive strategies, and for disease prognosis and prediction, is an important step toward precision medicine. However, for complex diseases, precision medicine is associated with several challenges. There is a significant heterogeneity between patients of a specific disease-both with regards to symptoms and underlying causal mechanisms-and the number of underlying genetic and nongenetic risk factors is often high. Here, we summarize precision medicine approaches for complex diseases and highlight the current breakthroughs as well as the challenges. We conclude that genomic-based precision medicine has been used mainly for patients with highly penetrant monogenic disease forms, such as cardiomyopathies. However, for most complex diseases-including psychiatric disorders and allergies-available polygenic risk scores are more probabilistic than deterministic and have not yet been validated for clinical utility. However, subclassifying patients of a specific disease into discrete homogenous subtypes based on molecular or phenotypic data is a promising strategy for improving diagnosis, prediction, treatment, prevention, and prognosis. The availability of high-throughput molecular technologies, together with large collections of health data and novel data-driven approaches, offers promise toward improved individual health through precision medicine.
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| 4. |
- Lim, Che Kang, et al.
(författare)
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Reversal of Immunoglobulin. A Deficiency in Children
- 2015
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Ingår i: Journal of Clinical Immunology. - : Springer Science and Business Media LLC. - 0271-9142 .- 1573-2592. ; 35:1, s. 87-91
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Tidskriftsartikel (refereegranskat)abstract
- Immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in the general population. It is defined as a serum IgA level below or equal to 0.07 g/l with normal IgM and IgG levels in children over the age of 4. However, a few cases of reversal of IgAD at later ages have been observed previously, especially in pediatric patients. This study aimed at investigating the frequency of reversal in a large cohort of children and young adults in order to evaluate the present definition of IgAD. Clinical laboratory records from 654 pediatric IgA deficient patients, 4-13 years of age, were retrieved from five university hospitals in Sweden. Follow up in the children where IgA serum levels had been routinely measured was subsequently performed. In addition, follow up of the IgA-levels was also performed at 4, 8 and 16 years of age in children who were IgA deficient at the age of 4 years in a Swedish population-based birth cohort study in Stockholm (BAMSE). Nine out of 39 (23.1 %) children who were identified as IgAD at 4 years of age subsequently increased their serum IgA level above 0.07 g/L. The average age of reversal was 9.53 +/- 2.91 years. In addition, 30 out of the 131 (22.9 %) children with serum IgAD when sampled between 5 and 9.99 years of age reversed their serum IgA level with time. The BAMSE follow up study showed a reversal of IgAD noted at 4 years of age in 8 out of 14 IgAD children at 16 years of age (5 at 8 years of age) where 4 were normalized their serum IgA levels while 4 still showed low serum levels of IgA, yet above the level defining IgAD. The results indicate that using 4 years of age, as a cut off for a diagnosis of IgAD may not be appropriate. Our findings suggest that a diagnosis of IgAD should not be made before the early teens using 0.07 g/L of IgA in serum as a cut off.
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| 5. |
- Melén, Erik, et al.
(författare)
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Precisionsmedicin kan bli viktig även vid komplexa sjukdomar
- 2021
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Ingår i: Lakartidningen. - 0023-7205. ; 118
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Tidskriftsartikel (refereegranskat)abstract
- Complex diseases represent a number of common disorders such as allergic conditions, cardiovascular, metabolic and chronic inflammatory diseases. These diseases are caused by a combination of genetic, environmental and lifestyle factors. This complex etiology creates challenges when it comes to diagnostics, follow-up programs and treatment. Although exact disease mechanisms are yet to be elucidated for most complex diseases, key genetic determinants have been mapped and omics profiling has unraveled involved pathways. Using this wealth of data, precision medicine applications have started to appear also for common, complex diseases. In this article, we review current precision medicine applications from a clinical point of view and outline briefly a roadmap ahead for further clinical implementation of precision medicine in complex diseases.
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| 6. |
- Melén, Erik, et al.
(författare)
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Short-acting β2 -agonist use and asthma exacerbations in Swedish children: A SABINA Junior study.
- 2022
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Ingår i: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - : Wiley. - 1399-3038 .- 0905-6157. ; 33:11
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Tidskriftsartikel (refereegranskat)abstract
- In adults and adolescents with asthma, use of ≥3 short-acting β2 -agonist (SABA) canisters/year is associated with increased exacerbation risk. Whether this association is present in younger children remains unknown. In this SABA use IN Asthma (SABINA) Junior study, we assessed the association of SABA collection with exacerbation risk in the general Swedish pediatric asthma population.This population-based cohort study utilized linked data from the Swedish national healthcare registries involving patients with asthma (<18years) treated in secondary care between 2006-2015. Exacerbation risk, by baseline SABA collection (0-2 vs. ≥3 canisters, further examined as ordinal/continuous variable) and stratified on comorbid atopic disease (allergic rhinitis, dermatitis and eczema, and food/other allergies), was assessed for 1-year follow-up using negative binomial regression.Of 219,561 patients assessed, 45.4%, 31.7%, and 26.5% of patients aged 0-5, 6-11, and 12-17years, respectively, collected ≥3 SABA canisters during the baseline year (high use). Collection of ≥3 SABA canisters (vs. 0-2) was associated with increased exacerbation risk during follow-up (incidence rate ratios [95% confidence interval]: 1.35 [1.29-1.42], 1.22 [1.15-1.29], and 1.26 [1.19-1.34] for 0-5-, 6-11-, and 12-17-year-olds, respectively); the association persisted with SABA as a continuous variable and was stronger among patients without atopic diseases (32%-44% increased risk versus. 14%-21% for those with atopic disease across groups).High SABA use was associated with increased asthma exacerbation risk in children, particularly in those without comorbid atopic diseases, emphasizing the need for asthma medication reviews and reformative initiatives by caregivers and healthcare providers on SABA use.
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| 7. |
- Middeldorp, Christel M., et al.
(författare)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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| 8. |
- Thunqvist, Per, et al.
(författare)
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Lung function after extremely preterm birth-A population-based cohort study (EXPRESS)
- 2018
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Ingår i: Pediatric Pulmonology. - : Wiley. - 8755-6863 .- 1099-0496. ; 53:1, s. 64-72
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Follow-up studies of children and young adults born very-to-moderately preterm show persistent and significant lung function deficits. The aim of the study was to determine lung function and airway mechanics in school-aged children born in 2004 to 2007 and extremely preterm (after 22-26 weeks of gestation).METHODS: In a population-based cohort of children born extremely preterm and controls born at term (n = 350), follow-up at 6½-years-of-age was performed using spirometry and impulse oscillometry. Associations to gestational age, smallness for gestational age (SGA), and bronchopulmonary dysplasia (BPD) were assessed.RESULTS: Children born extremely preterm had lower forced vital capacity (FVC, z-score: -0.7, 95%CI: -1.0;-0.4), forced expiratory volume (FEV1 , z-score: -1.1, 95%CI: -1.4; -0.8), higher frequency-dependence of resistance (R5-20 , 0.09, 95%CI: 0.05; 0.12 kPa · L-1 · s-1 ) and larger area under the reactance curve (AX, 0.78, 95%CI: 0.49; 1.07 kPa · L-1 ) than controls. In children born at 22-24 weeks of gestation, 24% had FVC and 44% had FEV1 below the lower limit of normal. SGA and severe BPD only marginally contributed to pulmonary outcomes. Asthma-like disease was reported in 40% of extremely preterm children and 15% of controls.CONCLUSION: Many children born extremely preterm have altered airway mechanics and significant obstructive reduction in lung function. This warrants consideration for treatment and continued follow-up.
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| 9. |
- Zettergren, Anna, et al.
(författare)
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Assessing tobacco use in Swedish young adults from self-report and urinary cotinine : A validation study using the BAMSE birth cohort
- 2023
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Ingår i: BMJ Open. - 2044-6055. ; 13:7
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Studies on health effects of tobacco often rely on self-reported exposure data, which is subjective and can lead to misclassification. The aim of this study was to describe the prevalence of cigarette smoking, snus and e-cigarette use, as well as to validate self-reported tobacco use among young adults in Sweden. Method Participants of a population-based Swedish cohort (n=3052), aged 22-25 years, assessed their tobacco use in a web questionnaire. Urinary cotinine was analysed in a subsample of the study population (n=998). The agreement between self-reported tobacco use and urinary cotinine was assessed using Cohen's Kappa coefficient (κ) at a cut-off level of 50 ng/mL. Results Patterns of tobacco use differed between men and women. Among men, 20.0% reported daily snus use, 5.8% daily cigarette smoking and 5.6% any e-cigarette use. In contrast, 3.2% of the women reported daily snus use, 9.0% daily cigarette smoking and 2.4% any e-cigarette use. Among the tobacco use categories, daily snus users had the highest levels of cotinine. Of reported non-tobacco users, 3.5% had cotinine levels above the cut-off, compared with 68.0% among both occasional cigarette smokers and snus users, 67.5% among all e-cigarette users and 94.7% and 97.8% among daily cigarette smokers and snus users, respectively. Agreement between self-reported tobacco use and urinary cotinine was classified as strong for daily use of cigarettes (κ=0.824) and snus (κ=0.861), while moderate to weak for occasional smoking (κ=0.618), occasional snus use (κ=0.573) and any e-cigarette use (κ=0.576). Conclusions We found high validity of self-reported tobacco use in our study population, particularly for daily tobacco use. Further, we found that daily snus users were exposed to high levels of cotinine. Together with previous findings, our results indicate good validity of self-reported tobacco use among young adults.
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| 10. |
- Zettergren, Anna, et al.
(författare)
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Exposure to environmental phthalates during preschool age and obesity from childhood to young adulthood
- 2021
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 192
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Tidskriftsartikel (refereegranskat)abstract
- Obesity rates are increasing globally, and recent theories suggest that phthalates may contribute to obesity development. This longitudinal study aimed to investigate associations between environmental phthalate exposure during childhood and obesity, utilizing data from 100 participants from a Swedish birth cohort. The participants were followed repeatedly from birth and provided spot urine samples at 4 years. Weight and height were measured at ages 4, 8, 16 and 24 years, as well as additional anthropometric indices at 24 years. Urine samples were analysed for 10 phthalate metabolites using liquid chromatography tandem mass spectrometry. Generalized estimating equation models were performed to assess overall and age-specific associations between urinary phthalate concentrations and BMI groups; thin/normal weight vs overweight/obese. After adjustment for potential confounders, overall associations were observed for diisononyl phthalate (DiNP) metabolites mono(oxo-isononyl) phthalate (MOiNP) (OR per increase ng/ml: 1.18; 95% CI: 1.05, 1.33), mono(carboxy-isooctyl) phthalate (MCiOP) (OR: 1.06; 95% CI: 1.01, 1.11) and ∑DiNP (OR: 1.02; 95% CI:1.00, 1.04) and development of overweight/obesity up to age 24 years. Age-specific associations were observed for the same metabolites at 8, 16 and 24 years. Furthermore, linear regression analysis revealed associations between increased body fat % at age 24 years and MHiNP (β: 2.42; 95% CI: 0.44, 4.39), MOiNP (β: 2.32; 95% CI: 0.46, 4.18), MCiOP (β: 2.65; 95% CI: 0.41, 4.89) and ∑DiNP (β: 2.65; 95% CI: 0.52, 4.77). These findings suggest that DiNP exposure during preschool age may be associated with subsequent obesity, however these findings need to be corroborated by further research.
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