Clinical implications of airway obstruction with normal or low FEV1 in childhood and adolescence.

BACKGROUND: Airway obstruction is defined by spirometry as a low forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio. This impaired ratio may originate from a low FEV1 (classic) or a normal FEV1 in combination with a large FVC (dysanaptic). The clinical implications of dysanaptic obstruction during childhood and adolescence in the general population remain unclear. AIMS: To investigate the association between airway obstruction with a low or normal FEV1 in childhood and adolescence, and asthma, wheezing and bronchial hyperresponsiveness (BHR). METHODS: In the BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology; Sweden) and PIAMA (Prevention and Incidence of Asthma and Mite Allergy; the Netherlands) birth cohorts, obstruction (FEV1:FVC ratio less than the lower limit of normal, LLN) at ages 8, 12 (PIAMA only) or 16 years was classified as classic (FEV1

Quality of Life and Bidirectional Gut-Brain Interactions in Irritable Bowel Syndrome From Adolescence to Adulthood.

BACKGROUNDS AND AIMS: Reports on cross-sectional and longitudinal associations between health-related quality of life (HRQoL), psychological distress, and irritable bowel syndrome (IBS) in the adolescent and young adult general population are few. We aimed to describe cross-sectional associations between HRQoL and IBS in adolescence and young adulthood, and examine bidirectional gut-brain interactions in the transition from childhood to adulthood. METHODS: We included 3391 subjects from a prospective birth cohort study, with data on IBS at 16 years of age and 24 years of age. IBS was assessed using the pediatric Rome III (16 years of age) and the adult Rome IV (24 years of age) diagnostic questionnaires. HRQoL and psychological distress were assessed through EQ-5D. Sex-adjusted logistic regression models were used to examine associations between overall HRQoL/psychological distress at 16 years of age and new-onset IBS at 24 years of age (brain-gut) and between IBS at 16 years of age and new-onset psychological distress at 24 years of age (gut-brain). RESULTS: In subjects with vs without IBS at 16 and 24 years of age, overall HRQoL (EQ visual analog scale, EQ-5D index value) was lower, and it was more common reporting problems in 4 of 5 EQ-5D dimensions (all P < .05). EQ-5D index value at 16 years of age was inversely associated (odds ratio [OR], 0.1, 95% confidence interval [CI], 0.01-0.6), and psychological distress at 16 years of age was positively associated (OR, 1.6; 95% CI, 1.2-2.3), with new-onset IBS at 24 years of age. Having any abdominal pain-related disorder of gut-brain interaction at 16 years of age was associated with new-onset psychological distress at 24 years of age (OR, 1.7; 95% CI, 1.2-2.5). CONCLUSIONS: Adolescents and young adults with IBS in the general population have impaired HRQoL. Bidirectional gut-brain interactions are relevant for symptom generation in abdominal pain-related disorders of gut-brain interaction, and for HRQoL impairment and psychological distress in the transition from childhood to adulthood.

Natural course of pollen-induced allergic rhinitis from childhood to adulthood: A 20-year follow up.

BACKGROUND: Allergic rhinitis (AR) is one of the most common chronic diseases worldwide. There are limited prospective long-term data regarding persistency and remission of AR. The objective of this study was to investigate the natural course of pollen-induced AR (pollen-AR) over 20 years, from childhood into early adulthood. METHODS: Data from 1137 subjects in the Barn/Children Allergi/Allergy Milieu Stockholm Epidemiologic birth cohort (BAMSE) with a completed questionnaire regarding symptoms, asthma, treatment with allergen immunotherapy (AIT) and results of allergen-specific IgE for inhalant allergens at 4, 8, 16 and 24 years were analyzed. Pollen-AR was defined as sneezing, runny, itchy or blocked nose; and itchy or watery eyes when exposed to birch and/or grass pollen in combination with allergen-specific IgE ≥0.35kUA/L to birch and/or grass. RESULTS: Approximately 75% of children with pollen-AR at 4 or 8 years had persistent disease up to 24 years, and 30% developed asthma. The probability of persistency was high already at low levels of pollen-specific IgE. The highest rate of remission from pollen-AR was seen between 16 and 24 years (21.5%); however, the majority remained sensitized. This period was also when pollen-specific IgE-levels stopped increasing and the average estimated annual incidence of pollen-AR decreased from 1.5% to 0.8% per year. CONCLUSION: Children with pollen-AR are at high risk of persistent disease for at least 20 years. Childhood up to adolescence seems to be the most dynamic period of AR progression. Our findings underline the close cross-sectional and longitudinal relationship between sensitization, AR and asthma.

Epidemiology of mastocytosis: a population-based study (Sweden).

BACKGROUND: Mastocytosis is a disease characterized by accumulation of aberrant mast cells and mediator-related symptoms and is divided into systemic mastocytosis (SM) and cutaneous mastocytosis (CM). The epidemiology of mastocytosis remains incompletely understood. OBJECTIVE: To estimate the incidence, prevalence, overall survival (OS) and burden of comorbidities in adult mastocytosis patients identified in Swedish population-based registries. METHODS: Individuals (≥ 20 years of age) with a mastocytosis diagnosis in the National Patient Register (NPR) and/or the Swedish Cancer Register (SCR) between 2001 and 2018, were identified. In a matched cohort design, for each case five randomly selected mastocytosis-free comparators matched on age, sex, and county of residence were chosen from the Population Register. The Kaplan-Meier method was used to compare OS between individuals with mastocytosis and comparators. Information on concomitant disease at baseline was assessed by use of the Charlson Comorbidity Index (CCI). RESULTS: We identified 2,040 adults with a mastocytosis diagnosis yielding an annual incidence of 1.56 per 100,000 (95% CI 1.29-1.87) and a prevalence of 23.9 per 100,000 (95% CI 22.8-25.0). The comorbidity burden was higher, and the OS lower, in patients with mastocytosis compared to comparators. INTERPRETATION: We found a higher incidence and prevalence of mastocytosis compared to assessments in other settings and confirmed that the prognosis generally is favorable. Of special note was evidence of a higher comorbidity burden in mastocytosis patients compared to the background population. LIMITATIONS: Underreporting and inconsistencies in the use of diagnostic codes.

Circulating CC16 and Asthma: A Population-based, Multicohort Study from Early Childhood through Adult Life.

Rationale: Club cell secretory protein (CC16) is an antiinflammatory protein highly expressed in the airways. CC16 deficiency has been associated with lung function deficits, but its role in asthma has not been established conclusively. Objectives: To determine 1) the longitudinal association of circulating CC16 with the presence of active asthma from early childhood through adult life and 2) whether CC16 in early childhood predicts the clinical course of childhood asthma into adult life. Methods: We assessed the association of circulating CC16 and asthma in three population-based birth cohorts: the Tucson Children's Respiratory Study (years 6-36; total participants, 814; total observations, 3,042), the Swedish Barn/Children, Allergy, Milieu, Stockholm, Epidemiological survey (years 8-24; total participants, 2,547; total observations, 3,438), and the UK Manchester Asthma and Allergy Study (years 5-18; total participants, 745; total observations, 1,626). Among 233 children who had asthma at the first survey in any of the cohorts, baseline CC16 was also tested for association with persistence of symptoms. Measurements and Main Results: After adjusting for covariates, CC16 deficits were associated with increased risk for the presence of asthma in all cohorts (meta-analyzed adjusted odds ratio per 1-SD CC16 decrease, 1.20; 95% confidence interval [CI], 1.12-1.28; P < 0.0001). The association was particularly strong for asthma with frequent symptoms (meta-analyzed adjusted relative risk ratio, 1.40; 95% CI, 1.24-1.57; P < 0.0001), was confirmed for both atopic and nonatopic asthma, and was independent of lung function impairment. After adjustment for known predictors of persistent asthma, children with asthma in the lowest CC16 tertile had a nearly fourfold increased risk for having frequent symptoms persisting into adult life compared with children with asthma in the other two CC16 tertiles (meta-analyzed adjusted odds ratio, 3.72; 95% CI, 1.78-7.76; P < 0.0001). Conclusions: Circulating CC16 deficits are associated with the presence of asthma with frequent symptoms from childhood through midadult life and predict the persistence of asthma symptoms into adulthood. These findings support a possible protective role of CC16 in asthma and its potential use for risk stratification.

Plasticity of Individual Lung Function States from Childhood to Adulthood.

Rationale: Recent evidence highlights the importance of optimal lung development during childhood for health throughout life. Objectives: To explore the plasticity of individual lung function states during childhood. Methods: Prebronchodilator FEV1 z-scores determined at age 8, 16, and 24 years in the Swedish population-based birth cohort BAMSE (Swedish abbreviation for Child [Barn], Allergy, Milieu, Stockholm, Epidemiological study) (N = 3,069) were used. An unbiased, data-driven dependent mixture model was applied to explore lung function states and individual state chains. Lung function catch-up was defined as participants moving from low or very low states to normal or high or very high states, and growth failure as moving from normal or high or very high states to low or very low states. At 24 years, we compared respiratory symptoms, small airway function (multiple-breath washout), and circulating inflammatory protein levels, by using proteomics, across states. Models were replicated in the independent Dutch population-based PIAMA (Prevention and Incidence of Asthma and Mite Allergy) cohort. Measurements and Main Results: Five lung function states were identified in BAMSE. Lung function catch-up and growth failure were observed in 74 (14.5%) BAMSE participants with low or very low states and 36 (2.4%) participants with normal or high or very high states, respectively. The occurrence of catch-up and growth failure was replicated in PIAMA. Early-life risk factors were cumulatively associated with the very low state, as well as with catch-up (inverse association) and growth failure. The very low state as well as growth failure were associated with respiratory symptoms, airflow limitation, and small airway dysfunction at adulthood. Proteomics identified IL-6 and CXCL10 (C-X-C motif chemokine 10) as potential biomarkers of impaired lung function development. Conclusions: Individual lung function states during childhood are plastic, including catch-up and growth failure.

Paediatric asthma hospitalisations continue to decrease in Finland and Sweden between 2015 and 2020.

We previously reported a decreasing incidence of paediatric asthma hospitalisations in Finland, but a rather stable trend in Sweden, between 2005 and 2014. We now aimed to investigate the incidence of paediatric asthma hospitalisations in these countries between 2015 and 2020, using Finland's National Hospital Discharge Register and Sweden's National Patient Register, which cover all hospitalisations in the respective countries. From 2015 to 2019, the incidence of paediatric asthma hospitalisations decreased by 36.7% in Finland and by 39.9% in Sweden and are increasingly approaching parity. In 2020, despite differences in COVID-19-related restrictions, asthma hospitalisations decreased by over 40%, thus warranting future research on the subject.

Associations of improved air quality with lung function growth from childhood to adulthood: the BAMSE study.

BACKGROUND: The beneficial effect of improving air quality on lung function development remains understudied. We assessed associations of changes in ambient air pollution levels with lung function growth from childhood until young adulthood in a Swedish cohort study. METHODS: In the prospective birth cohort BAMSE (Children, Allergy, Environment, Stockholm, Epidemiology (in Swedish)), spirometry was conducted at the 8-year (2002-2004), 16-year (2011-2013) and 24-year (2016-2019) follow-ups. Participants with spirometry data at 8 years and at least one other measurement in subsequent follow-ups were included (1509 participants with 3837 spirometry measurements). Ambient air pollution levels (particulate matter with diameter ≤2.5 µm (PM2.5), particulate matter with diameter ≤10 µm (PM10), black carbon (BC) and nitrogen oxides (NO x )) at residential addresses were estimated using dispersion modelling. Linear mixed effect models were used to estimate associations between air pollution exposure change and lung function development. RESULTS: Overall, air pollution levels decreased progressively during the study period. For example, the median (interquartile range (IQR)) level of PM2.5 decreased from 8.24 (0.92) µg·m-3 during 2002-2004 to 5.21 (0.67) µg·m-3 during 2016-2019. At the individual level, for each IQR reduction of PM2.5 the lung function growth rate increased by 4.63 (95% CI 1.64-7.61) mL per year (p<0.001) for forced expiratory volume in 1 s and 9.38 (95% CI 4.76-14.00) mL per year (p<0.001) for forced vital capacity. Similar associations were also observed for reductions of BC and NO x . Associations persisted after adjustment for potential confounders and were not modified by asthma, allergic sensitisation, overweight, early-life air pollution exposure or dietary antioxidant intake. CONCLUSIONS: Long-term reduction of air pollution is associated with positive lung function development from childhood to young adulthood.

Exploring proteomic plasma biomarkers in eosinophilic and neutrophilic asthma.

BACKGROUND: Few biomarkers identify eosinophilic and neutrophilic asthma beyond cell concentrations in blood or sputum. Finding novel biomarkers for asthma endotypes could give insight about disease mechanisms and guide tailored treatment. Our aim was to investigate clinical characteristics and inflammation-related plasma proteins in relation to blood eosinophil and neutrophil concentrations in subjects with and without asthma. METHODS: We included 24-26-year-old subjects (n = 2063) from the Swedish population-based cohort BAMSE. Subjects with asthma (n = 239) and without asthma (n = 1824) were subdivided based on blood eosinophil and neutrophil concentrations (cut-offs 0.3 × 109 /L and 5.0 × 109 /L, respectively). We measured the levels of 92 plasma proteins using Olink Proseek Multiplex Inflammation Panel Assay. Group statistics tests were used to analyse the data, as well as adjusted multiple logistic regression models. RESULTS: Among subjects with asthma, 21.8% had eosinophilic asthma and 20.5% neutrophilic asthma. Eosinophilic asthma, but not neutrophilic asthma, was associated with a distinct clinical phenotype with, for example, higher proportions of eczema and sensitization. Most plasma proteins that associated with high eosinophil and/or neutrophil blood concentrations in subjects with asthma showed similar associations in subjects without asthma. However, out of these proteins, MMP10 levels were associated with eosinophilic asthma and were significantly higher as compared to controls with high eosinophilic concentration, while CCL4 levels associated with high neutrophil concentration only in subjects with asthma. CONCLUSIONS: Eosinophilic asthma was associated with a clear clinical phenotype. With our definitions, we identified MMP10 as a possible plasma biomarker for eosinophilic asthma and CCL4 was linked to neutrophilic asthma. These proteins should be evaluated further in clinical settings and using sputum granulocytes to define the asthma endotypes.

Dietary patterns, lung function and asthma in childhood: a longitudinal study.

BACKGROUND: Longitudinal epidemiological data are scarce examining the relationship between dietary patterns and respiratory outcomes in childhood. We investigated whether three distinct dietary patterns in mid-childhood were associated with lung function and incident asthma in adolescence. METHODS: In the Avon Longitudinal Study of Parents and Children, 'processed', 'traditional', and 'health-conscious' dietary patterns were identified using principal components analysis from food frequency questionnaires at 7 years of age. Post-bronchodilator forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and forced expiratory flow at 25-75% of FVC (FEF25-75) were measured at 15.5 years and were transformed to z-scores based on the Global Lung Function Initiative curves. Incident asthma was defined by new cases of doctor-diagnosed asthma at age 11 or 14 years. RESULTS: In multivariable-adjusted models, the 'health-conscious' pattern was positively associated with FEV1 (regression coefficient comparing top versus bottom quartile of pattern score 0.16, 95% CI 0.01 to 0.31, P for trend 0.04) and FVC (0.18, 95% CI 0.04 to 0.33, P for trend 0.02), while the 'processed' pattern was negatively associated with FVC (- 0.17, 95% CI - 0.33 to - 0.01, P for trend 0.03). Associations between the 'health-conscious' and 'processed' patterns and lung function were modified by SCGB1A1 and GPX4 gene polymorphisms. We found no evidence of an association between the 'traditional' pattern and lung function, nor between any pattern and FEF25-75 or incident asthma. CONCLUSIONS: A 'health-conscious' diet in mid-childhood was associated with higher subsequent lung function, while a diet high in processed food was associated with lower lung function.

Development of sensitization to peanut and storage proteins and relation to markers of airway and systemic inflammation: A 24-year follow-up.

BACKGROUND: Long-time data of peanut allergy over time is sparse. We aimed to study the longitudinal development of sensitization to peanut extract and storage protein allergen molecules and associations with asthma status, airway and systemic inflammation markers. METHODS: The Swedish birth cohort BAMSE followed 4089 participants with questionnaires, clinical investigations and blood sampling between 0 and 24 years. Information on (i) background factors at 2 months, (ii) peanut allergy symptoms and IgE data (ImmunoCAP) at 4, 8, 16, and 24 years, and (iii) IgE to storage proteins, lung function data including exhaled nitric oxide (FENO) as well as systemic inflammatory markers at 24 years of age were collected. RESULTS: The prevalence of peanut extract sensitization, defined as IgE ≥ 0.35 kUA /L, was 5.4%, 8.0%, 7.5%, and 6.2% at 4, 8, 16, and 24 years of age, respectively. Between 8 and 24 years of age, (33/1565) participants developed IgE-ab to peanut extract (median 1,4, range 0.7-2.6 kUA /L), and among those 85% were also sensitized to birch. Only six individuals developed sensitization to Ara h 2 (≥0.1 kUA /L) between 8 and 24 years of age, of whom three had an IgE-ab level between 0.1-0.12 kUA /L. Storage protein sensitization was associated with elevated FENO, blood eosinophils and type 2 inflammation-related systemic proteins. CONCLUSION: Sensitization to peanut extract after 4 years of age is mainly induced by birch cross-sensitization and IgE to Ara h 2 rarely emerges after eight years of age. Storage protein sensitization is associated with respiratory and systemic inflammation.

Allergic disease trajectories up to adolescence: Characteristics, early-life, and genetic determinants.

BACKGROUND: Allergic diseases often develop jointly during early childhood but differ in timing of onset, remission, and progression. Their disease course over time is often difficult to predict and determinants are not well understood. OBJECTIVES: We aimed to identify trajectories of allergic diseases up to adolescence and to investigate their association with early-life and genetic determinants and clinical characteristics. METHODS: Longitudinal k-means clustering was used to derive trajectories of allergic diseases (asthma, atopic dermatitis, and rhinitis) in two German birth cohorts (GINIplus/LISA). Associations with early-life determinants, polygenic risk scores, food and aeroallergen sensitization, and lung function were estimated by multinomial models. The results were replicated in the independent Swedish BAMSE cohort. RESULTS: Seven allergic disease trajectories were identified: "Intermittently allergic," "rhinitis," "early-resolving dermatitis," "mid-persisting dermatitis," "multimorbid," "persisting dermatitis plus rhinitis," and "early-transient asthma." Family history of allergies was more prevalent in all allergic disease trajectories compared the non-allergic controls with stronger effect sizes for clusters comprising more than one allergic disease (e.g., RRR = 5.0, 95% CI = [3.1-8.0] in the multimorbid versus 1.8 [1.4-2.4] in the mild intermittently allergic cluster). Specific polygenic risk scores for single allergic diseases were significantly associated with their relevant trajectories. The derived trajectories and their association with genetic effects and clinical characteristics showed similar results in BAMSE. CONCLUSION: Seven robust allergic clusters were identified and showed associations with early life and genetic factors as well as clinical characteristics.

Health-related quality of life decreases in young people with asthma during the transition from adolescence to young adulthood: a birth cohort study.

BACKGROUND: During the transition from paediatric to adult healthcare there is a gap between asthma guidelines and actual management with decreased healthcare consultations and dispensations of asthma medications after the transition to adult healthcare among young people with asthma. How health-related quality of life (HRQoL) develops during the transition from adolescence to young adulthood is unclear. Our aim was therefore to investigate HRQoL among young people with asthma during the transition to adulthood. Further, to assess if level of asthma control and physical activity influence any potential association between asthma and HRQoL. METHODS: The study population consisted of 2268 participants from the ongoing Swedish population-based prospective birth cohort BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology). HRQoL was measured using the instrument EQ-5D-3 L and three general questions. The EQ-5D-3 L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3 L instrument and questions on general health, symptoms and treatment of asthma, and lifestyle factors were based on data from follow-ups at 16 and 24 years. Cross-sectional analyses were made. RESULTS: At the 24-year follow-up, the adjusted median values of EQ VAS were lower compared with at the 16-year follow-up; among both participants with asthma (80 vs. 85, p < 0.01) and those without asthma (80 vs. 87, p < 0.01). At the 24-year follow-up, participants with uncontrolled asthma had a lower adjusted median EQ VAS score than peers with controlled/partly controlled asthma (75 vs. 80, p = 0.03). Further, young adults with asthma who did not fulfil the WHO recommendations on physical activity had lower EQ VAS scores than peers who did (70 vs. 80, p < 0.01). CONCLUSION: HRQoL is lower in young adulthood than in adolescence. Young adults with asthma having uncontrolled disease or who are physically inactive appear to be particularly vulnerable.

Changes in lifestyle, adiposity, and cardiometabolic markers among young adults in Sweden during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has impacted on public health in several ways. The aim of the study was to investigate changes in lifestyle, adiposity, and cardiometabolic markers among young adults in Sweden during the COVID-19 pandemic and their determinants. METHODS: The study included 1 004 participants from the population-based birth cohort BAMSE. Anthropometrics, body composition (bioelectric impedance analyses), pulse, and blood pressure were measured before (December 2016-May 2019; mean age 22.6 years) and during (October 2020-June 2021; mean age 25.7 years) the COVID-19 pandemic. Lifestyle changes during the pandemic were assessed through a questionnaire. RESULTS: All measures of adiposity (weight, BMI, body fat percentage, trunk fat percentage) and cardiometabolic markers (blood pressure, pulse) increased during the study period (e.g., body fat percentage by a median of + 0.8% in females, p < 0.001, and + 1.5% in males, p < 0.001). Male sex, non-Scandinavian ethnicity, BMI status (underweight and obesity), and changes in lifestyle factors, e.g., decreased physical activity during the pandemic, were associated with higher increase in BMI and/or adiposity. CONCLUSION: Lifestyle factors, adiposity and cardiometabolic markers may have been adversely affected among young adults in Sweden during the COVID-19 pandemic compared with the preceding years. Targeted public health measures to reduce obesity and improve healthy lifestyle are important to prevent future non-communicable diseases.

SARS-CoV-2-specific B- and T-cell immunity in a population-based study of young Swedish adults.

BACKGROUND: Young adults are now considered major spreaders of coronavirus disease 2019 (COVID-19) disease. Although most young individuals experience mild to moderate disease, there are concerns of long-term adverse health effects. The impact of COVID-19 disease and to which extent population-level immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exists in young adults remain unclear. OBJECTIVE: We conducted a population-based study on humoral and cellular immunity to SARS-CoV-2 and explored COVID-19 disease characteristics in young adults. METHODS: We invited participants from the Swedish BAMSE (Barn [Children], Allergy Milieu, Stockholm, Epidemiology) birth cohort (age 24-27 years) to take part in a COVID-19 follow-up. From 980 participants (October 2020 to June 2021), we here present data on SARS-CoV-2 receptor-binding domain-specific IgM, IgA, and IgG titers measured by ELISA and on symptoms and epidemiologic factors associated with seropositivity. Further, SARS-CoV-2-specific memory B- and T-cell responses were detected for a subpopulation (n = 108) by ELISpot and FluoroSpot. RESULTS: A total of 28.4% of subjects were seropositive, of whom 18.4% were IgM single positive. One in 7 seropositive subjects was asymptomatic. Seropositivity was associated with use of public transport, but not with sex, asthma, rhinitis, IgE sensitization, smoking, or body mass index. In a subset of representative samples, 20.7% and 35.0% had detectable SARS-CoV-2 specific B- and T-cell responses, respectively. B- and T-cell memory responses were clearly associated with seropositivity, but T-cell responses were also detected in 17.2% of seronegative subjects. CONCLUSIONS: Assessment of IgM and T-cell responses may improve population-based estimations of SARS-CoV-2 infection. The pronounced surge of both symptomatic and asymptomatic infections among young adults indicates that the large-scale vaccination campaign should be continued.

Fruit, vegetable and dietary antioxidant intake in school age, respiratory health up to young adulthood.

BACKGROUND: Dietary antioxidants may protect the lung against oxidative damage and prevent chronic respiratory disease. We aimed to investigate fruit, vegetable and antioxidant intake (measured as total antioxidant capacity, TAC) at age 8 years in relation to asthma and lung function up to 24 years. METHODS: In this study of 2506 participants from a Swedish birth cohort, diet was assessed using food frequency questionnaires. Information on asthma was collected by questionnaires, and lung function was measured by spirometry at ages 8, 16 and 24 years. Generalized estimating equations and mixed effect models were used to assess overall, age- and sex-specific associations. RESULTS: After adjustment for confounders, a higher fruit intake at age 8 years was associated with a tendency to reduced odds of prevalent asthma (T3 vs. T1, OR 0.78; 95% CI 0.60-1.01, p-trend .083), with reduced odds of incident asthma and increased odds of remittent asthma (≥median, OR 0.76; 95% CI 0.58-0.99 and OR 1.60; 95% CI 1.05-2.42, respectively) up to 24 years. Comparable, but non-significant, odds ratios were observed in analyses of long-term fruit intake (mean intake at ages 8 and 16 years). In contrast, no association was observed with vegetable intake. A higher dietary TAC (T3 vs. T1) at 8 years was associated with reduced odds of prevalent asthma (OR 0.73; 95% CI 0.58-0.93, p-trend .010) and improved lung function development (FEV1 -z +0.11; 95% CI 0.01-0.21, p-trend .036 and FVC-z +0.09; 95% CI -0.01-0.20, p-trend .072) up to 24 years. Associations were more pronounced among males, and regarding asthma, participants sensitized to aeroallergens. CONCLUSIONS: Antioxidant intake in school age may improve asthma and lung function up to young adulthood. Although our results should be interpreted with caution, they emphasize the importance of following current dietary guidelines regarding consumption of antioxidant-rich foods as part of a balanced diet.

Mefloquine causes selective mast cell apoptosis in cutaneous mastocytosis lesions by a secretory granule-mediated pathway.

Mastocytosis is a KIT-related myeloproliferative disease characterised by abnormal expansion of neoplastic mast cells (MC) in the skin or virtually any other organ system. The cutaneous form of adult-onset mastocytosis is almost invariably combined with indolent systemic involvement for which curative therapy is yet not available. Here we evaluated a concept of depleting cutaneous MCs in mastocytosis lesions ex vivo by targeting their secretory granules. Skin biopsies from mastocytosis patients were incubated with or without mefloquine, an antimalarial drug known to penetrate into acidic organelles such as MC secretory granules. Mefloquine reduced the number of dermal MCs without affecting keratinocyte proliferation or epidermal gross morphology at drug concentrations up to 40 µM. Flow cytometric analysis of purified dermal MCs showed that mefloquine-induced cell death was mainly due to apoptosis and accompanied by caspase-3 activation. However, caspase inhibition provided only partial protection against mefloquine-induced cell death, indicating predominantly caspase-independent apoptosis. Further assessments revealed that mefloquine caused an elevation of granule pH and a corresponding decrease in cytosolic pH, suggesting drug-induced granule permeabilisation. Extensive damage to the MC secretory granules was confirmed by transmission electron microscopy analysis. Further, blockade of granule acidification or serine protease activity prior to mefloquine treatment protected MCs from apoptosis, indicating that granule acidity and granule-localised serine proteases play major roles in the execution of mefloquine-induced cell death. Altogether, these findings reveal that mefloquine induces selective apoptosis of MCs by targeting their secretory granules and suggest that the drug may potentially extend its range of medical applications.

Preterm birth reduces the risk of IgE sensitization up to early adulthood: A population-based birth cohort study.

BACKGROUND: Immunoglobulin E (IgE) sensitization is associated with asthma and allergic diseases. Gestational age influences early immune system development, thereby potentially affecting the process of tolerance induction to allergens. OBJECTIVE: To study IgE sensitization to common allergens by gestational age from childhood up to early adulthood. METHODS: Population-based birth cohort, data from the Swedish BAMSE study were used. Allergen-specific IgE antibodies to a mix of common food (fx5) and inhalant (Phadiatop) allergens were analysed at 4, 8, 16 and 24 years. Sensitization was defined as allergen-specific IgE ≥0.35 kUA /L to fx5 and/or Phadiatop at each time point. Using logistic regression and generalized estimated equations, adjusted odds ratios (aORs) for sensitization in relation to gestational age were calculated. Replication was sought within the Swedish twin study STOPPA. RESULTS: In BAMSE, 3522 participants were screened for IgE antibodies during follow-up; of these, 197 (5.6%) were born preterm (<37 gestational weeks) and 330 (9.4%) post-term (≥42 weeks). Preterm birth reduced the risk of sensitization to common food and/or inhalant allergens up to early adulthood by 29% (overall aOR = 0.71; 95% CI: 0.52-0.98), and to food allergens specifically by 40% (overall aOR = 0.60; 95% CI: 0.38-0.93). No relation was found between post-term birth and IgE sensitization at any time point. Replication analyses in STOPPA (N = 675) showed similar risk estimates for sensitization to food and/or inhalant allergens (aOR = 0.72; 95% CI: 0.42-1.21), which resulted in a combined meta-analysis aOR = 0.71 (95% CI: 0.54-0.94). CONCLUSIONS: Our study suggests an inverse association between preterm birth and long-term IgE sensitization.

Adapting a South African social innovation for maternal peer support to migrant communities in Sweden: a qualitative study.

INTRODUCTION AND AIM: Social and health disparities persist in Sweden despite a high quality and universally accessible welfare system. One way of bridging social gaps is through social innovations targeting the most vulnerable groups. The South African Philani model, a social innovation for peer support aimed at pregnant women and mothers of young children, was adapted to the local context in southern Sweden. This study aimed to document and analyze the process of adapting the Philani model to the Swedish context. METHODS: Eight semi-structured interviews and three workshops were held with eleven stakeholders and peer supporters in the implementing organization and its steering committee. The data were analyzed using thematic analysis. RESULTS: The analysis resulted in five main themes and fifteen sub-themes representing different aspects of how the peer support model was contextualized. The main themes described rationalizations for focusing on social determinants rather than health behaviors, using indirect mechanisms and social ripple effects to achieve change, focusing on referring clients to established public and civil society services, responding to a heterogeneous sociocultural context by recruiting peer supporters with diverse competencies, and having a high degree of flexibility in how contact was made with clients and how their needs were met. CONCLUSION: The South African Philani model was contextualized to support socially disadvantaged mothers and expectant mothers among migrant communities in Sweden. In the process, adaptations of the intervention's overall focus, working methods, and recruitment and outreach strategies were motivated by the existing range of services, the composition of the target group and the conditions of the delivering organization. This study highlights various considerations that arise when a social innovation developed in a low- or middle-income context is implemented in a high-income context.

Non-adherence and sub-optimal treatment with asthma medications in young adults: a population-based cohort study.

OBJECTIVE: Pharmacological treatment plays a key role in the management of asthma, but medication adherence is generally low. Our aim was to assess factors associated with dispensing patterns of, and adherence to, asthma medication in young adults with asthma. METHODS: The study included young adults (age 22-24 years) from the Swedish population-based birth cohort BAMSE (n = 3,064) with linkage to register data on dispensed asthma medications and recorded diagnosis. Dispensing information was collected in January 2014-June 2019 (the study period) to cover the period of questionnaire data. Adherence to asthma medication was defined as refilling a prescription within 18 months. RESULTS: In total, 234 individuals (7.6%) had asthma (doctor's diagnosis of asthma in combination with respiratory symptoms) and had been dispensed at least one prescription of asthma medication during the study period. Among them, 77% were dispensed a controller medication. The mean number of prescriptions dispensed per individual was higher in males than females (11.0 vs. 7.2; p < 0.01). The proportion of asthmatics with only a short-acting ß2-agonist (SABA) dispensed was 22%, of which 33% were classified as having uncontrolled asthma. Adherence to controller medication was 60% and higher among those with an asthma diagnosis from specialized care than those diagnosed in primary care (RR 1.32 95% CI 1.03-1.69). Sex, socioeconomic status, and non-allergic comorbidity did not affect adherence. CONCLUSION: Young adults with asthma had few prescriptions of asthma medication dispensed, indicating sub-optimal treatment. A considerable proportion was dispensed only SABA. Furthermore, adherence to controller medication was relatively low.