Anna Bergström

Background: The long‐term prognosis of childhood asthma remains uncertain. We aimed to (1) assess the prevalence of asthma remission from childhood to young adulthood, (2) identify associated factors, and (3) evaluate whether symptom‐based remission was related to objective markers of inflammation and lung function. Materials and Methods: We analyzed data from 2698 participants in the Swedish population‐based BAMSE birth cohort, followed up to age 24 years with questionnaires and clinical examinations. Symptom‐based remission was defined as absence of asthma symptoms and medication in the preceding year. Clinical remission also required no hospital visits and optimization of lung function (postbronchodilator forced expiratory volume in 1 s ≥ 80%). Complete remission required normal eosinophil counts (< 0.3 × 10 ⁹ /L) and fractional exhaled nitric oxide levels (< 40 ppb). Results: Among 257 participants with asthma at age 8 years, 39% achieved symptom‐based remission, 29% clinical remission, and 18% complete remission at age 24 years. Male sex increased the likelihood of symptom‐based remission (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.3–4.5), whereas food sensitization (OR 0.3, 95% CI 0.3–0.6) and overweight/obesity (OR 0.4, 95% CI 0.2–0.9) decreased it. Among individuals in symptom‐based remission, 27% displayed abnormal results in at least one objective marker. Conclusions: Four of 10 participants with asthma in childhood achieved symptom‐based remission by young adulthood, but rates declined when stricter, objective definitions were applied. A substantial subset of individuals with symptom‐based remission still showed signs of type two inflammation or reduced lung function, indicating that absence of symptoms does not necessarily reflect complete disease resolution.

Background: In birth-cohort studies, response rates generally decline over time. We aimed to evaluate representativeness and identify predictors of retention up to young adulthood in a population-based birth cohort originally focused on asthma and allergies. Methods: The Barn/Child, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) birth cohort was established in 1994–6 in Stockholm, Sweden. We utilized data from questionnaires and Swedish registers to compare the characteristics of participants at age 24 years (n = 3064) with those of the original cohort (n = 4089) and the general population born in 1994–6 in Stockholm county (n = 68 378) and Sweden (n = 310 976). Logistic regression was used to identify predictors of retention at age 24 years. Results: The response rate declined over time and was higher in females than in males in adolescence and young adulthood (80.0% versus 70.0% at age 24 years). Compared with the original cohort, participants at age 24 years more often had dispensed asthma medications (6.6% versus 5.8%) and university education (52.6% versus 47.8%), but had less often a mother who smoked during pregnancy (9.6% versus 10.8%). Similar patterns were observed in comparisons with the general population. Female sex [odds ratio (OR) 1.75, 95% confidence interval (CI) 1.49–2.05] and high parental education (OR 1.33, 95% CI 1.12–1.59) were the predominant predictors of retention in the cohort. Conclusion: Female sex, higher socio-economic status, and asthma were predictive factors of retention in the cohort after 24 years. This may have influenced the observed prevalence rates of asthma and allergies, and associations between potential risk factors and outcomes associated with retention.

Background: Dietary nitrate exposure originates from vegetables and drinking water, and is, together with nitrite, used as food additives in animal products. Both compounds can generate N-nitroso compounds, some of which are known animal carcinogens. However, epidemiological evidence regarding nitrate and nitrite intake in relation to colorectal cancer (CRC) risk and its subsites remains limited. Methods: Nitrate and nitrite intake was assessed by linking a food and drinking water database to food frequency questionnaires completed in 1997 and updated in 2009 and 2019, by 82 009 middle-aged to elderly men and women of 2 population-based cohorts from the Swedish Infrastructure for Medical Population-based Life-course and Environmental Research. We ascertained incident CRC through the Swedish Cancer Registry from 1998 to 2022. Cox proportional hazards models were fitted to evaluate exposure-outcome associations, presented as hazard ratios (HR) with 95% confidence intervals (CI). Results: We ascertained 3170 CRC cases. No associations were observed for nitrate intake with CRC. In contrast, when comparing the highest with the lowest quintile, nitrite intake was associated with a dose-dependent higher risk of CRC in men (HR 1.23; 95% CI = 1.06 to 1.43; Ptrend < .05) but not in women. CRC subsite analyses in men indicated the strongest association for distal colon cancer (HR 1.50; 95% CI = 1.13 to 1.98). Conclusion: A higher nitrite intake was associated with a higher CRC risk in men, particularly distal colon cancer. These findings indicate potential sex differences and differential susceptibilities across the colorectum in nitrite-related cancer risk.

Background: Antibiotic resistance is a global health crisis that is not solely explained by antibiotics usage. However, environmental and lifestyle contributions to antimicrobial resistance (AMR) in children are not well understood, especially compared to adults. As the gut functions as a reservoir for antibiotic resistance genes (ARGs), the aim of this study was to better understand the influence of lifestyle on the gut microbiome and resistome using shotgun-metagenomic sequencing data of Swedish children from the PARSIFAL (Prevention of Allergy Risk factors for Sensitization In children related to Farming and Anthroposophic Lifestyle) study. Results: Farm children exhibited high proportions of unique bacterial species and differentially abundant ARGs linked to the farm environment, and similar differences were found in anthroposophic children. Age, breastfeeding duration, and obesity significantly influenced the overall resistance load, independently of lifestyle. Despite limited statistical power, our findings suggest that lifestyle and environment both shape the microbiome and resistome of children. Conclusions: This study corroborates the possible influence of the farm environment on the gut microbiome and resistome, revealing a highly individualized repertoire of low-abundance microbes and ARGs in farm children. Additionally, associations of age, obesity and the duration of exclusive breastfeeding with ARG load were found in a currently understudied age range. Overall, this study raises the need for further research on rare species and ARGs as well as their transmission dynamics in relation to the environment.

Population-based studies of circulating blood proteins have provided profound insights into human biology. However, short-lived changes often remained undetected. To address this, we performed a comprehensive longitudinal dried blood spot (DBS) self-sampling study in 808 young adults of the BAMSE cohort during 2020-2022. We profiled serological, autoimmune, and proteomic phenotypes in relation to SARS-CoV-2 exposures (infection, vaccination), physiological traits, genetic variation, and blood counts. Data-driven seroclustering revealed dynamic immune response to both exposures, while analysis of anti-interferon autoantibodies (AAbs) uncovered associations of pre-existing stable AAbs with prolonged COVID-19 symptoms. Genome-wide mapping determined 664 pQTLs, with cis-pQTLs associated showing increased longitudinal stability. We also identified relationships between blood cell counts and DBS proteins beyond the hematocrit effects. Paired pre- and post-exposure highlighted transient alterations for infection (e.g. LAP3) and vaccinations (e.g. TIMP3). Multi-molecular phenotyping in self-sampling can capture dynamic immune trajectories, informing precision medicine efforts with clinically valuable insights on short-term variability in health phenotypes.

The human blood proteome provides a holistic readout of health states through the assessment of thousands of circulating proteins. In this study, we present a pan-disease resource to enable the study of diverse disease phenotypes within a harmonized proteomics dataset. By profiling protein concentrations across 59 diseases and healthy cohorts, we identified proteins associated with age, sex, and body mass index, as well as disease-specific signatures. This study highlights shared and distinct protein patterns across conditions, demonstrating the power of a unified proteomics approach to uncover biological insights. The dataset, covering 8262 individuals and up to 5416 proteins, serves as an online resource for exploring disease-specific protein profiles and advancing precision medicine research.

Background Antibiotic resistance is a global health crisis that is not solely explained by antibiotics usage. However, environmental and lifestyle contributions to antimicrobial resistance (AMR) in children are not well understood, especially compared to adults. As the gut functions as a reservoir for antibiotic resistance genes (ARGs), the aim of this study was to better understand the influence of lifestyle on the gut microbiome and resistome using shotgun-metagenomic sequencing data of Swedish children from the PARSIFAL (Prevention of Allergy Risk factors for Sensitization In children related to Farming and Anthroposophic Lifestyle) study. Results Farm children exhibited high proportions of unique bacterial species and differentially abundant ARGs linked to the farm environment, and similar differences were found in anthroposophic children. Age, breastfeeding duration, and obesity significantly influenced the overall resistance load, independently of lifestyle. Despite limited statistical power, our findings suggest that lifestyle and environment both shape the microbiome and resistome of children. Conclusions This study corroborates the possible influence of the farm environment on the gut microbiome and resistome, revealing a highly individualized repertoire of low-abundance microbes and ARGs in farm children. Additionally, associations of age, obesity and the duration of exclusive breastfeeding with ARG load were found in a currently understudied age range. Overall, this study raises the need for further research on rare species and ARGs as well as their transmission dynamics in relation to the environment.

Background: Protein quantitative trait loci (pQTLs) remain underexplored in asthma but might provide valuable insights into the underlying molecular mechanisms. This study aimed to investigate associations between genetic variation and inflammation‐related plasma proteins and to assess differences in the levels of genetically determined proteins in subjects with signatures of type‐2 inflammation and/or asthma.Methods: A pQTL mapping of 92 inflammation‐related plasma proteins was conducted in young adults from the Swedish BAMSE cohort (n = 1538). Replication of sentinel pQTLs was attempted, and the overlap and colocalization of pQTLs with expression quantitative trait loci (eQTLs) were investigated using publicly available data. Proteins with significant pQTLs were tested for association with type‐2 signatures defined as high levels of fractional exhaled nitric oxide, blood eosinophils, and/or sensitization to airborne allergens in subjects with or without asthma in BAMSE.Results: Forty‐five sentinel pQTLs (33 cis, 12 trans) for 39 inflammation‐related proteins were identified (p ≤ 7.14 × 10⁻¹¹), and a high proportion of these were validated in independent populations. A high likelihood for colocalization of cis‐pQTLs and cis‐eQTLs was observed for 19 proteins in different tissues. Six of the 39 circulating proteins with significant pQTLs were associated with type‐2 signatures and/or asthma, and matrix metalloproteinase‐10 (MMP‐10) showed the most significant associations.Conclusions: These findings underscore the existence of a genetic component influencing the plasma levels of proteins involved in inflammatory processes, including MMP‐10, which is suggested to have a role in high type‐2 inflammation in asthma subjects.