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Mechanistic research suggests that lifestyle and environmental factors impact respiratory health across generations by epigenetic changes transmitted through male germ cells. Evidence from studies on humans is very limited.We investigated multigeneration causal associations to estimate the causal effects of tobacco smoking on lung function within the paternal line. We analysed data from 383 adult offspring (age 18-47 years; 52.0% female) and their 274 fathers, who had participated in the European Community Respiratory Health Survey (ECRHS)/Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study and had provided valid measures of pre-bronchodilator lung function. Two counterfactual-based, multilevel mediation models were developed with: paternal grandmothers' smoking in pregnancy and fathers' smoking initiation in prepuberty as exposures; fathers' forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), or FEV1/FVC z-scores as potential mediators (proxies of unobserved biological mechanisms that are true mediators); and offspring's FEV1 and FVC, or FEV1/FVC z-scores as outcomes. All effects were summarised as differences (Δ) in expected z-scores related to fathers' and grandmothers' smoking history.Fathers' smoking initiation in prepuberty had a negative direct effect on both offspring's FEV1 (Δz-score -0.36, 95% CI -0.63- -0.10) and FVC (-0.50, 95% CI -0.80- -0.20) compared with fathers' never smoking. Paternal grandmothers' smoking in pregnancy had a negative direct effect on fathers' FEV1/FVC (-0.57, 95% CI -1.09- -0.05) and a negative indirect effect on offspring's FEV1/FVC (-0.12, 95% CI -0.21- -0.03) compared with grandmothers' not smoking before fathers' birth nor during fathers' childhood.Fathers' smoking in prepuberty and paternal grandmothers' smoking in pregnancy may cause lower lung function in offspring. Our results support the concept that lifestyle-related exposures during these susceptibility periods influence the health of future generations.

Objective: The aim of this systematic review and meta-analysis was to assess the association between e-cigarette use and subsequent initiation or recurrence of cigarette smoking.

Data sources: A systematic literature search was finalised on 11 November 2019 using PubMed (including MEDLINE), EMBASE, Cochrane Library, Scopus, PubMed Health, NICE Evidence Search, PROSPERO, CRD and PsycInfo.

Study selection: Studies were included if meeting the following criteria: reporting empirical results; longitudinal observational design with a minimum of 3 months of follow-up; including general population samples; allowing for the comparison between users and nonusers of e-cigarettes. Studies rated as having high risk of bias were excluded. Studies were independently assessed by at least two authors. The procedures described by PRISMA were followed, and the quality of evidence was rated using GRADE.

Data synthesis: 30 longitudinal studies from 22 different cohorts assessing e-cigarette use among nonsmokers or never-smokers at baseline, and subsequent use of cigarette smoking at follow-up, were included in this review. A random-effects meta-analysis based on 89076 participants showed a pooled unadjusted odds ratio (OR) of cigarette smoking among baseline nonsmoker e-cigarette users compared with nonusers of 4.68 (CI 3.64–6.02), while the adjusted OR was 3.37 (CI 2.68–4.24). These results were consistent irrespective of whether the outcome was measured as ever-smoking or as past 30-day smoking. The evidence was graded as moderate.

Conclusions: Use of e-cigarettes may predict the initiation or recurrence of cigarette smoking.

The Arctic Monitoring Assessment Program (AMAP) is tasked with monitoring and assessing the status of environmental contaminants in the Arctic, documenting levels and trends, and producing science-based assessments. The objectives of this paper are to present the current levels of persistent organic pollutants (POPs) across the Arctic, and to identify trends and knowledge gaps as detailed in the most recent AMAP Human Health Assessment Report. Many Arctic populations continue to have elevated levels of these contaminants, and the highest levels of POPs were observed in populations from Greenland, Faroe Islands, and Nunavik (Canada), as well as populations in the coastal Chukotka district (Russia) for legacy POPs only. Concentrations of most POPs are declining in Arctic populations in regions where time trends data exist, although the declines are not consistent across all regions. The exceptions are per- and polyfluoroalkyl substances, with concentrations of some long-chain PFAS such as perfluorononanoic acid increasing in populations in Nunavik, Greenland and Sweden. This paper provides a more extensive summary of levels of contaminants in adults, pregnant women, and children across the Arctic than previous AMAP human health assessments, particularly for levels of long-chain PFAS, which are currently under consideration for inclusion in the Stockholm Convention.

The 2021 Arctic Monitoring Assessment Program (AMAP)’s Human Health Assessment report presents a summary of the presence of contaminants in human populations across the circumpolar Arctic and provides an update to the previous assessment released in 2015. The primary objective of this paper is to summarise some of these findings by describing the current levels of metals across the Arctic, including key regional and temporal trends based on available national data and literature, and highlight knowledge gaps. Many Arctic populations continue to have elevated levels of these contaminants, and the highest levels of mercury (Hg) were observed in populations from Greenland, Faroe Islands, and Nunavik (Canada). Still, concentrations of several metals are declining in Arctic populations in regions where time trends data exist, although the declines are not consistent across all regions. The 2021 AMAP human health assessment report and this paper provide an extensive summary of levels of metals and trace elements in adults, pregnant women, and children across the Arctic.

Exposure to mercury (Hg) is a global concern, particularly among Arctic populations that rely on the consumption of marine mammals and fish which are the main route of Hg exposure for Arctic populations.The MercuNorth project was created to establish baseline Hg levels across several Arctic regions during the period preceding the Minamata Convention. Blood samples were collected from 669 pregnant women, aged 18–44 years, between 2010 and 2016 from sites across the circumpolar Arctic including Alaska (USA), Nunavik (Canada), Greenland, Iceland, Norway, Sweden, Northern Lapland (Finland) and Murmansk Oblast (Russia). Descriptive statistics were calculated, multiple pairwise comparisons were made between regions, and unadjusted linear trend analyses were performed.Geometric mean concentrations of total Hg were highest in Nunavik (5.20 µg/L)  and Greenland (3.79 µg/L), followed by Alaska (2.13 µg/L), with much lower concentrations observed in the other regions (ranged between 0.48 and 1.29 µg/L). In Nunavik, Alaska and Greenland, blood Hg concentrations have decreased significantly since 1992, 2000 and 2010 respectively with % annual decreases of 4.7%, 7.5% and 2.7%, respectively.These circumpolar data combined with fish and marine mammal consumption data can be used for assessing long-term Hg trends and the effectiveness of the Minamata Convention.

Background: The prevalence of atopic dermatitis (AD) has increased over several decades and now affects about one-fifth of all children in high-income countries (HICs). While the increase continues in lower-income countries, the prevalence of AD might have reached a plateau in HICs.

Objectives: To investigate trends in the prevalence of AD and atopic comorbidity in schoolchildren in Sweden.

Methods: The study population consisted of three cohorts of children (median age 8 years) in Norrbotten, Sweden, for 1996 (n = 3430), 2006 (n = 2585) and 2017 (n = 2785). An identical questionnaire that included questions from the International Study of Asthma and Allergies in Childhood (ISAAC) protocol was used in all three cohorts. Trends in AD prevalence were estimated, as well as trends in atopic comorbidity. AD prevalence was estimated both according to the ISAAC definition of AD and by adding the reported diagnosis by a physician (D-AD).

Results: The prevalence of AD decreased in the last decade, from 22.8% (1996) and 21.3% (2006) to 16.3% (2017; P < 0.001). The prevalence of D-AD was lower, but the same pattern of decrease was seen, from 9.3% (1996) and 9.4% (2006) to 5.7% (2017; P < 0.001). In all three cohorts, AD was more common among girls than boys (18.9% vs. 13.8% in 2017; P < 0.001). Children from the mountain inlands had a higher prevalence of AD than children from coastal cities (22.0% vs. 15.1% in 2017; P < 0.001). In comparing D-AD, there were no significant differences between the sexes or between inland or coastal living. Concomitant asthma increased over the years from 12.2% (1996) to 15.8% (2006) to 23.0% (2017; P < 0.001). Concomitant allergic rhinitis and allergic sensitization increased from 1996 (15.0% and 27.5%) to 2006 (24.7% and 49.5%) but then levelled off until 2017 (21.0% and 46.7%).

Conclusions: The prevalence of AD among schoolchildren in Sweden decreased over the study period, whereas atopic comorbidity among children with AD increased. Although a decrease was seen, AD is still common and the increase in atopic comorbidity among children with AD, especially the increase in asthma, is concerning.

Recommendations aimed at protecting the public from toxicity of essential elements including essential metals have usually been developed separately from those recommendations aimed at protection from deficiency. Because of the uncertainties involved in the evaluations, these recommendations have sometimes been in conflict, emphasizing the need for a new approach, including a balanced consideration of nutritional and toxicological data. In developing these new principles of evaluation, some basic concepts based on interindividual variability in sensitivity to deficiency and toxicity must be considered. Such variation translates into one interval of (low) daily intakes, at which there is a risk of developing deficiency, and another interval of (high) dietary intakes at which toxicity may occur. In most instances, there is a third set of intakes in between, which represents the acceptable range of oral intake (AROI), in which no adverse effects occur. This range determined from a homeostatic or biologically based (BBM) approach, which is discussed here, would be expected to apply to the general population. It must be noted, however, that this range would not protect all persons from adverse effects: this applies to those with genetically determined sensitivity, who may require higher intakes to avoid deficiency or lower intakes to avoid toxicity than those defined by the AROI. Nonetheless, AROI could be derived to protect 95% of the general human population from minimal adverse effects of deficiency or toxicity arising from inadequate and excessive intakes. As such the correspondence of these values to current Health-Based Guidance Values (HBGVs) and reference intakes of essential metals (EMs), and the roles of the BBM/Homeostatic Approach in Risk Assessment of EMs are of important public health interest.

BACKGROUND & AIMS: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

METHODS: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs.

RESULTS: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80-0.96; P_trend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; P_trend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; P_trend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78-0.95; P_trend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18-1.45; P_trend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (P_{heterogeneity} = .026).

CONCLUSIONS: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.

Epidemiologic studies examining the association between specific fatty acids and colorectal cancer (CRC) risk are inconclusive. We investigated the association between dietary estimates and plasma levels of individual and total saturated (SFA), monounsaturated (MUFA), industrial-processed trans (iTFA), and ruminant-sourced trans (rTFA) fatty acids, and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Baseline fatty acid intakes were estimated in 450 112 participants (6162 developed CRC, median follow-up = 15 years). In a nested case-control study, plasma phospholipid fatty acids were determined by gas chromatography in 433 colon cancer cases and 433 matched controls. Multivariable-adjusted hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were computed using Cox and conditional logistic regression, respectively. Dietary total SFA (highest vs lowest quintile, HRQ5vsQ1 = 0.80; 95%CI:0.69-0.92), myristic acid (HRQ5vsQ1 = 0.83, 95%CI:0.74-0.93) and palmitic acid (HRQ5vsQ1 = 0.81, 95%CI:0.70-0.93) were inversely associated with CRC risk. Plasma myristic acid was also inversely associated with colon cancer risk (highest vs lowest quartile, ORQ4vsQ1 = 0.51; 95%CI:0.32-0.83), whereas a borderline positive association was found for plasma stearic acid (ORQ4vsQ1 = 1.63; 95%CI:1.00-2.64). Dietary total MUFA was inversely associated with colon cancer (per 1-SD increment, HR1-SD = 0.92, 95%CI: 0.85-0.98), but not rectal cancer (HR1-SD = 1.04, 95%CI:0.95-1.15, Pheterogeneity = 0.027). Dietary iTFA, and particularly elaidic acid, was positively associated with rectal cancer (HR1-SD = 1.07, 95%CI:1.02-1.13). Our results suggest that total and individual saturated fatty acids and fatty acids of industrial origin may be relevant to the aetiology of CRC. Both dietary and plasma myristic acid levels were inversely associated with colon cancer risk, which warrants further investigation.

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.

Background: 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.

Methods: 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.

Findings: Across the ten included studies, we included 243 465 European participants (mean age 51·4 years, 95% CI 51·4–51·5) in our analysis, of whom 136 275 (56·0%) were female and 107 190 (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).

Interpretation: 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. Funding: The European Respiratory Society, AstraZeneca, Chiesi Farmaceutici, GlaxoSmithKline, Menarini, and Sanofi-Genzyme.

Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer mainly caused by asbestos exposure. Specific and sensitive noninvasive biomarkers may facilitate and enhance screening programs for the early detection of cancer. We investigated DNA methylation (DNAm) profiles in MPM prediagnostic blood samples in a case-control study nested in the European Prospective Investigation into Cancer and nutrition (EPIC) cohort, aiming to characterise DNAm biomarkers associated with MPM. From the EPIC cohort, we included samples from 135 participants who developed MPM during 20 years of follow-up and from 135 matched, cancer-free, controls. For the discovery phase we selected EPIC participants who developed MPM within 5 years from enrolment (n = 36) with matched controls. We identified nine differentially methylated CpGs, selected by 10-fold cross-validation and correlation analyses: cg25755428 (MRI1), cg20389709 (KLF11), cg23870316, cg13862711 (LHX6), cg06417478 (HOOK2), cg00667948, cg01879420 (AMD1), cg25317025 (RPL17) and cg06205333 (RAP1A). Receiver operating characteristic (ROC) analysis showed that the model including baseline characteristics (age, sex and PC1wbc) along with the nine MPM-related CpGs has a better predictive value for MPM occurrence than the baseline model alone, maintaining some performance also at more than 5 years before diagnosis (area under the curve [AUC] < 5 years = 0.89; AUC 5-10 years = 0.80; AUC >10 years = 0.75; baseline AUC range = 0.63-0.67). DNAm changes as noninvasive biomarkers in prediagnostic blood samples of MPM cases were investigated for the first time. Their application can improve the identification of asbestos-exposed individuals at higher MPM risk to possibly adopt more intensive monitoring for early disease identification.

Objectives: This study aimed to analyze any reported antibiotic use for children aged <5 years with fever, diarrhea or cough with fast or difficult breathing (outcome) from low-income and middle-income countries (LMICs) during 2005–2017 by user characteristics: rural/urban residence, maternal education, household wealth, and healthcare source visited.

Methods: Based on 132 demographic and health surveys and multiple indicator cluster surveys from 73 LMICs, the outcome by user characteristics for all country-years was estimated using a hierarchical Bayesian linear regression model.

Results: Across LMICs during 2005–2017, the greatest relative increases in the outcome occurred in rural areas, poorest quintiles and least educated populations, particularly in low-income countries and South-East Asia. In low-income countries, rural areas had a 72% relative increase from 17.8% (Uncertainty Interval (UI): 5.2%–44.9%) in 2005 to 30.6% (11.7%–62.1%) in 2017, compared to a 29% relative increase in urban areas from 27.1% (8.7%–58.2%) in 2005 to 34.9% (13.3%–67.3%) in 2017. Despite these increases, the outcome was consistently highest in urban areas, wealthiest quintiles, and populations with the highest maternal education.

Conclusion: These estimates suggest that the increasing reported antibiotic use for sick children aged <5 years in LMICs during 2005–2017 was driven by gains among groups often underserved by formal health services.

Aim: There has been a lack of population‐based longitudinal data on serum ferritin in very low birth weight (VLBW) infants during hospitalisation. Our aim was to fill this gap in the knowledge and investigate risk factors for elevated serum ferritin and associations between erythrocyte transfusions and longitudinal growth.

Methods: We retrospectively reviewed longitudinal data on 126 VLBW infants treated at Umeå University Hospital, Sweden, between 2010‐2013.

Results: The infants’ mean gestational age and birth weight were 26.9 weeks and 899 grams. Most (91%) received erythrocyte transfusions and the majority had multiple erythrocyte transfusions. There was a significant correlation between serum ferritin and the volume of transfusions. Almost two‐thirds had at least one serum ferritin measurement of more than 350 µg/L, indicating iron overload. In those with complete anthropometric data (n=78) there was no significant effect of serum ferritin concentrations in relation to longitudinal growth, but there was a positive association between the erythrocyte transfusion dose and longitudinal growth in VLBW infants born before 25 weeks.

Conclusion: This is the first population‐based study to investigate longitudinal data on serum ferritin in VLBW infants during hospitalisation. The unexpected positive finding in the subgroup born at less than 25 weeks needs further research with a larger cohort.

Introduction: Self-rated health (SRH) offers insights into the evolving health demographics of an ageing population.

Aim: To assess change in SRH from old age to very old age and their associations with health and well-being factors, and to investigate the association between SRH and survival.

Methods: All participants in the MONICA 1999 re-examination born before 1940 (n = 1595) were included in the Silver-MONICA baseline cohort. The Silver-MONICA follow-up started in 2016 included participants in the Silver-MONICA baseline cohort aged 80 years or older. Data on SRH was available for 1561 participants at baseline with 446 of them also participating in the follow-up. The follow-up examination included a wide variety of measurements and tests.

Findings: Most participants rated their health as "Quite good" (54.5 %) at baseline. Over the study period, 42.6 % had stable SRH, 40.6 % had declined, and 16.8 % had improved. Changes in SRH were at follow-up significantly associated with age, pain, nutrition, cognition, walking aid use, self-paced gait speed, lower extremity strength, independence in activities of daily living, weekly physical exercise, outdoor activity, participation in organized activities, visiting others, morale, and depressive symptoms. SRH at baseline was significantly associated with survival (p < 0.05).

Conclusion: This study demonstrates associations between changes in SRH and a multitude of health- and wellbeing-related factors, as well as a relation between survival and SRH, accentuating their relevance within the ageing population.

Aim: to update the knowledge on the epidemiology of asthma with onset in childhood and adulthood as well as examine the importance of risk factors in early childhood and clinical characteristics on the incidence and prognosis of asthma.

Methods: The thesis is based on the epidemiological research program Obstructive Lung Disease in Northern Sweden (OLIN) studies. Pediatric cohort: recruited in 1996 (age 8y, n=3430, 97% of invited) and followed annually by questionnaire about asthma, allergy and risk factors until 19y and a postal questionnaire at 28y. Clinical examinations included skin prick tests (SPT at 8, 12 and 19y) and spirometry (19y). Adult cohort: 309 adults (age 20–60y) with asthma onset in the last 12 months were recruited 1995-99 and re-examined in 2012-14 (n=205). Structured interviews, spirometry and SPT were performed at recruitment and follow-up and bronchial hyperreactivity (BHR) at recruitment.

Results: The asthma incidence rate was 10-13/1000/year in childhood and adolescence and 6/1000/year in young adulthood. Several risk factors in early life were associated with asthma onset in childhood, adolescence and young adulthood, e.g. family history of asthma, <3 months breastfeeding, rhinoconjunctivitis and positive SPT at 8y, while low birthweight, maternal smoking during pregnancy, severe respiratory infections and eczema were associated with onset in childhood and adolescence. Among those with asthma at 8y, 62% still had asthma at 28y and this was associated with positive SPT, rhinoconjunctivitis, severe respiratory infection in childhood, and bronchial hyperreactivity (BHR) in adolescence. Coexistence of asthma, rhinitis and eczema increased by age, especially among those with a positive SPT. However, having all three conditions was uncommon. In the 15y follow-up adult onset asthma, 89% had persistent asthma. Better lung function at recruitment and less severe BHR was associated with remission. Remission rate of adult onset asthma was <1% per year.

Conclusion: The incidence of asthma was high during childhood and adolescence and then decreased in young adulthood. Factors in early life that were associated with incident asthma during childhood were still associated with the incidence in adult age. Among those with asthma onset by 8 years, 62%, still had asthma as young adults. The coexistence of asthma, rhinitis and eczema varied from 8 to 28y without following a specific pattern, only a small proportion reported having all three conditions. Remission of adult onset asthma was rare. 

Background: Although remission occur, childhood-onset asthma may persist until adulthood. Since few longitudinal population-based studies have followed a cohort from childhood until adulthood, the knowledge on predictors of persistence of asthma is sparse.

Aim: To estimate persistence of asthma from 8 to 28 years and its associated factors. Methods: Within the OLIN (Obstructive Lung Disease in Northern Sweden) studies, a cohort was recruited in 1996 (age 8y, n = 3430) and followed annually with questionnaires about asthma and risk factors until 19y. Clinical examinations included skin prick tests (at 8, 12 and 19y) and lung function tests (17 and 19y) whereof a subsample performed bronchial hyperreactivity test. We identified n = 248 with asthma at 8y whereof 170 (69%) participated in a follow-up at 28y (73% of possible to invite).

Results: Of the 170 participants at 28y, 105 (61.8%) had persistent asthma (women: 49/76, 64.5%; men: 56/94, 59.6%, p = 0.513). Factors collected at recruitment: allergic sensitization (OR7.8, 95%CI 3.0–20.2), severe respiratory infection (OR2.6, 95%CI 1.1–6.3) and higher asthma severity score (OR1.6, 95%CI 1.1–2.4) were associated with asthma at 28y after adjustment for sex, family history of asthma, breastfeeding <3 months and eczema. Replacing allergic sensitization with rhinoconjunctivitis in the model yielded OR3.4 (95%CI 1.5–8.0). Bronchial hyperreactivity at age 17y associated with asthma at 28y (OR9.0, 95%CI 1.7–47.0).

Conclusions: Among children with asthma onset by 8y, 62% still had asthma at age 28 years. Persistent asthma was associated with allergic sensitization, rhinoconjunctivitis, severe respiratory infection, a more severe asthma and bronchial hyperreactivity.

Background: There are few long-term clinical follow-up studies of adult-onset asthma. The aim of this article was to study clinical characteristics of adult-onset asthma in relation to remission and persistence of the disease in a 15-year follow-up.

Methods: A cohort of 309 adults aged 20-60 years with asthma onset during the last 12 months verified by bronchial variability, was recruited between 1995 and 1999 from the general population in northern Sweden. The cohort was followed-up in 2003 (n=250) and between 2012 and 2014 (n=205). Structured interviews and spirometry were performed at recruitment and the follow-ups. Bronchial hyperreactivity (BHR) and skin-prick tests were performed at recruitment and blood samples were collected at the last follow-up. Remission of asthma was defined as no asthma symptoms and no use of asthma medication during the last 12 months.

Results: Of eight individuals in remission in 2003, five had relapsed between 2012 and 2014 and in total, 23 (11%) were in remission, while 182 had persistent asthma. Those in remission had higher mean forced expiratory volume in 1 s % predicted at recruitment than those with persistent asthma (94.6 versus 88.3, p=0.034), fewer had severe BHR (27.3% versus 50.9%, p=0.037) and they had less body mass index increase (+1.6 versus +3.0, p=0.054). Of those with persistent asthma, 13% had uncontrolled asthma and they had higher levels of blood neutrophils than those with partly controlled or controlled asthma.

Conclusion: Higher forced expiratory volume in 1 s % predicted and less-severe BHR was associated with remission of adult-onset asthma, but still, the proportion in remission in this 15-year follow-up was low.

Background: Avoidance of pets as a strategy for preventing atopic diseases has been questioned. This study aimed to identify the risk of sensitization and allergic symptoms at age 13 in relation to dog‐ and cat‐keeping during and after the first year of life.

Methods: The study included all children born at Östersund Hospital in Northern Sweden between February 1996 and January 1997 (n = 1231). At inclusion, parents were asked to answer questionnaires about lifestyle, including cat‐ and dog‐keeping. Dog allergy, cat allergy, hay fever, and asthma were diagnosed based on parental reported allergic symptoms at 13 years of age (n = 834). The risks of sensitization or allergy in relation to dog‐ and cat‐keeping during and after the first year of life were analyzed with logistic regression. To adjust for reverse causation, all subjects that had reported avoidance of pets due to allergic symptoms of the child or allergy in the family (n = 177) were excluded.

Results: Dog‐ or cat‐keeping during the first year of life reduced the risk of sensitization to dog or cat allergens, respectively, and to birch and to at least one of the 10 allergens tested. Cat‐keeping, both during and after the first year of life, reduced the risk of cat allergy and hay fever. Having a dog at home during the first year of life reduced the risk of dog and cat allergy, whereas dog‐keeping after the first year of life did not affect allergic symptoms.

Conclusions: Cat ownership, either during or after the first year of life, may be a strategy for preventing the development of cat allergy and hay fever later in life. Dog ownership reduced the risk of sensitization to dog and birch allergen, and also the risk of cat and dog allergy, but had no effect on hay fever.

The COVID-19 pandemic has demonstrated the importance of unbiased, real-time statistics of trends in disease events in order to achieve an effective response. Because of reporting delays, real-time statistics frequently underestimate the total number of infections, hospitalizations and deaths. When studied by event date, such delays also risk creating an illusion of a downward trend. Here, we describe a statistical methodology for predicting true daily quantities and their uncertainty, estimated using historical reporting delays. The methodology takes into account the observed distribution pattern of the lag. It is derived from the "removal method"-a well-established estimation framework in the field of ecology.

Background: Physical activity is a useful means to improve symptoms and memory performance to some extent in individuals with stress-induced exhaustion disorder. Individuals in this group commonly do not need to reach the recommended levels of physical activity. Developing methods to support physical activity as a lasting behaviour is important.

Objective: The aim of the study was to explore the processes involved when using physical activity prescription as part of rehabilitation in a group context for individuals with stress-induced exhaustion disorder.

Method: A total of 27 individuals with stress-induced exhaustion disorder participated in six focus groups. The informants underwent a multimodal intervention including prescription of physical activity. The physical activity prescription had a cognitive behaviour approach and included information about physical activity, home assignments and goal setting. The data was analysed with grounded theory method using constant comparison.

Results: The analysis of the data was developed into the core category ‘trying to integrate physical activity into daily life in a sustainable way’, and three categories: ‘acceptance of being good enough’, ‘learning physical activity by doing’ and ‘advocation for physical activity in rehabilitation’. The informants identified that during the physical activity prescription sessions they learned what physical activity was, what was ‘good enough’ in terms of dose and intensity of physical activity, and how to listen to the body’s signals. These insights, in combination with performing physical activity during home assignments and reflecting with peers, helped them incorporate physical activity in a new and sustainable way. A need for more customised physical activity with the ability to adjust to individual circumstances was requested.

Conclusion: Prescription of physical activity in a group context may be a useful method of managing and adjusting physical activity in a sustainable way for individuals with stress-induced exhaustion disorder. However, identifying people who need more tailored support is important.

Background: Difference in dyspnea mMRC >= 2 between Finnish speaking and Swedish-speaking populations in Finland has not been previously studied.

Methods: In February 2016, a respiratory questionnaire was sent to 8000 randomly selected subjects aged 20-69 years in western Finland with a response rate of 52.3%. The registered native language of each subject determined whether questionnaire in Finnish or Swedish was applied. Multiple logistic regression was performed to calculate Odds Ratios (OR) with 95% CI for the simultaneous effects of independent variables on dyspnea mMRC >= 2.

Results: Of all participants, 2780 (71.9%) were Finnish speakers and 1084 (28.1%) were Swedish speakers. Finnish speakers had a higher prevalence of dyspnea mMRC >= 2 (11.1% vs 6.5% p < 0.001) when compared to Swedish speakers. Finnish speakers smoked more often, had higher BMI, spent less time moving during the day, had more often occupational exposure to vapours, gases, dusts or fumes (VGDF), and had lower socioeconomic status based on occupation. Significant risk factors for dyspnea mMRC >= 2 were COPD (OR = 10.94), BMI >35 (OR = 9.74), asthma (OR = 4.78), female gender (OR = 2.38), older age (OR = 2.20), current smoking (OR = 1.59), and occupational exposure to VGDF (OR = 1.47).

Conclusions: Swedish speakers had less dyspnea mMRC >= 2 which is explained by a healthier lifestyle. Smoking, obesity, and occupational exposures should be in focus to improve respiratory health.

It is important to examine how motorized traffic variables affect pedestrians along a gradient from rural to inner urban settings. Relations between pedestrians' perceptions of four traffic variables and appraisals of route environments as hindering-stimulating for walking as well as unsafe-safe for reasons of traffic, were therefore studied in the inner urban area of Stockholm, Sweden (n = 294). The pedestrians rated their perceptions and appraisals with the Active Commuting Route Environment Scale (ACRES). Correlation, multiple regression, and mediation analyses were used to study the relationships between the traffic variables and the outcome variables. Noise related negatively to both hindering-stimulating for walking, and to unsafety-safety for traffic reasons. Vehicle speed related negatively to unsafety-safety for traffic reasons. Furthermore, vehicle speed protruded as an important origin of the deterring effects of traffic among those who commute by foot. The study shows the value of both partial and simultaneous analyses of the effect of all four traffic variables in relation to outcome variables relevant for walking.

Background: Every walk takes place in a route environment, and it can play an important role in deterring or facilitating walking, and will always affect the environmental unwell-well-being of pedestrians. The aim of this study is to illuminate which the important route environmental variables are in this respect. The focus is, therefore, on pedestrians' perceptions of route environmental variables and how they relate to overall appraisals of route environments as hindering–stimulating for walking and unsafe–safe for reasons of traffic.

Methods: Commuting pedestrians in the inner urban area of Stockholm, Sweden (n = 294, 49.5 ± 10.4 years, 77% women), were recruited via advertisements. They evaluated their commuting route environments using a self-report tool, the Active Commuting Route Environment Scale (ACRES). Correlation, multiple regression, and mediation analyses were used to study the relationships between the variables and the outcome variables.

Results: Aesthetics and greenery appear to strongly stimulate walking, whereas noise, a proxy for motorized traffic, hinders it. Furthermore, aesthetics is positively related to traffic safety, whereas conflicts have the opposite role. Conflicts is an intermediate outcome, representing several basic environmental variables, some of which were directly and negatively related to unsafe–safe traffic.

Conclusion: Route environmental variables appear to be potent factors in deterring or facilitating walking. This knowledge is of importance for policymakers and urban planners when designing route environments with the aim of attracting new pedestrians, and simultaneously stimulating those who already walk to keep on.

Growing evidence indicates that air pollution can negatively impact cognitive functions. The olfactory system is interesting in this context as it is directly exposed to pollutants and also associated with cognitive functions. The aim of this study was to investigate long- and short-term PM_2.5 exposure in association with olfactory functions. Scores from odor tests were obtained from the Betula project - a longitudinal cohort study. Estimates of annual mean PM_2.5 concentrations at the participants' residential address were obtained from a dispersion-model. Daily mean PM_2.5 concentrations were obtained from a measuring station close to the test location. We found a positive association between long-term PM_2.5 exposure and odor identification, i.e. exposure was associated with a better ability to identify odors. We also found an interaction effect between PM_2.5 and age on odor identification. We found no associations between any PM_2.5 exposure and odor detection or between short-term PM_2.5 exposure and olfactory functions.

Background: Cigarette smoking and occupational exposures each have been reported to increase the risk of idiopathic pulmonary fibrosis (IPF), a disease previously considered of unknown origin. We investigated the risk of IPF mortality associated with combined smoking and occupational exposures.

Methods: A registry study of Swedish construction workers (N = 389,132), linked baseline smoking and occupational data with registry data on cause of death and hospital care diagnoses. Occupation was classified by the likelihood of exposure to vapors, gases, dusts, or fumes using a job-exposure matrix. Those likely exposed to asbestos or silica were excluded from the analysis. Age-adjusted relative risks [RRs] were calculated using Poisson regression. Follow-up observation began at age 40 and ended at age 89.

Results: Heavy smokers at baseline who were exposed to inorganic dusts during their working life had an increased risk of IPF mortality (RR 1.70; 95% confidence interval [CI] 1.11–2.60), while there was no statistically increased risk in the other exposure groups. There were dose–response relationships between smoking at baseline and IPF mortality among both unexposed and dust exposed workers, with similar risk for dust exposed and unexposed, except among baseline heavy smokers, where workers exposed to inorganic dust manifested the highest risk (RR 4.22; 95% CI 2.69–6.60). Excluding workers with chronic obstructive pulmonary disease or emphysema did not affect the results substantively.

Conclusion: A clear dose–response relationship was seen between smoking at baseline and IPF, supporting a causal relationship. Occupational exposure to inorganic dusts, excluding silica and asbestos, was associated with increased risk of IPF in baseline heavy current smokers.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) may exacerbate respiratory symptoms. A recent European Academy of Allergy and Clinical Immunology position paper recommended the use of an acronym, N-ERD (NSAID-exacerbated respiratory disease), for this hypersensitivity associated with asthma or chronic rhinosinusitis with or without nasal polyposis. Our aim was to estimate the prevalence of N-ERD and identify factors associated with N-ERD.

Methods: In 2016, a cross-sectional questionnaire survey of a random adult population of 16 000 subjects aged 20–69 years was performed in Helsinki and Western Finland. The response rate was 51.5%.

Results: The prevalence was 1.4% for N-ERD, and 0.7% for aspirin-exacerbated respiratory disease (AERD). The prevalence of N-ERD was 6.9% among subjects with asthma and 2.7% among subjects with rhinitis. The risk factors for N-ERD were older age, family history of asthma or allergic rhinitis, long-term smoking and exposure to environmental pollutants. Asthmatic subjects with N-ERD had a higher risk of respiratory symptoms, severe hypersensitivity reactions and hospitalisations than asthmatic subjects without N-ERD. The subphenotype of N-ERD with asthma was most symptomatic. Subjects with rhinitis associated with N-ERD, which would not be included in AERD, had the fewest symptoms.

Conclusion: We conclude that the prevalence of N-ERD was 1.4% in a representative Finnish adult population sample. Older age, family history of asthma or allergic rhinitis, cumulative exposure to tobacco smoke, secondhand smoke, and occupational exposures increased odds of N-ERD. N-ERD was associated with significant morbidity.

Purpose: Asthma is a heterogeneous disease, and factors associated with different asthma phenotypes are poorly understood. Given the higher prevalence of farming exposure and late diagnosis of asthma in more rural Western Finland as compared with the capital of Helsinki, we investigated the relationship between childhood farming environment and age at asthma diagnosis.

Methods: A cross-sectional population-based study was carried out with subjects aged 20– 69 years in Western Finland. The response rate was 52.5%. We included 3864 participants, 416 of whom had physician-diagnosed asthma at a known age and with data on the childhood environment. The main finding was confirmed in a similar sample from Helsinki. Participants were classified as follows with respect to asthma diagnosis: early diagnosis (0– 11 years), intermediate diagnosis (12–39 years), and late diagnosis (40–69 years).

Results: The prevalence of asthma was similar both without and with childhood exposure to a farming environment (11.7% vs 11.3%). Allergic rhinitis, family history of asthma, ex-smoker, occupational exposure, and BMI ≥ 30 kg/m2 were associated with a higher like-lihood of asthma. Childhood exposure to a farming environment did not increase the odds of having asthma (aOR, 1.10; 95% CI, 0.87–1.40). It did increase the odds of late diagnosis (aOR, 2.30; 95% CI, 1.12–4.69), but the odds were lower for early (aOR, 0.49; 95% CI, 0.30–0.80) and intermediate diagnosis of asthma (aOR, 0.75; 95% CI, 0.47–1.18).

Conclusion: Odds were lower for early diagnosis of asthma and higher for late diagnosis of asthma in a childhood farming environment. This suggests a new hypothesis concerning the etiology of asthma when it is diagnosed late.

Multimorbidity is an emerging public health priority. This study aims to assess the role of lifestyle and socioeconomic status in the prevalence of multimorbidity and chronic diseases by using two language groups that are part of the same genetic subgroup but differ by daily habits. We conducted a cross-sectional survey in 2016 with randomly selected population sample with 4173 responders (52.3%) aged 20–69 years in Western Finland. We included 3864 Finnish participants with Swedish (28.1%) or Finnish (71.9%) as a native language. We used a questionnaire to assess participants' chronic diseases and lifestyle. We determined multimorbidity as a disease count ≥ 2.

Finnish speakers were more likely to have a diagnosis of COPD, heart failure, diabetes, reflux disease, chronic kidney failure, and painful conditions than Swedish speakers. The prevalence of multimorbidity was higher for Finnish speakers in the age group of 60–69 years (41.0% vs. 32.0%, p = 0.018) than Swedish speakers. A higher proportion of Finnish speakers smoked, were obese, inactive, and had lower socioeconomic status compared to Swedish speakers. All these factors, in addition to age and female sex, were significant risk factors for multimorbidity. Prevalence of multimorbidity was different in two language groups living in the same area and was associated with differences in lifestyle factors such as smoking, physical inactivity and obesity.

The advent of heated tobacco products (HTPs) has introduced new variables in the study of nicotine delivery systems and their health implications. Amidst concerns over cardiovascular effects, this study aims to elucidate the acute impact of HTP inhalation on extracellular vesicles (EV) levels in young, healthy individuals. In this controlled, acute exposure study, 23 young, healthy volunteers were subjected to HTP inhalation. EV levels of endothelial and platelet origin were quantified through flow cytometry before and after exposure. Data analysis was performed using multiple measures ANOVA to assess changes in EV concentrations. Our findings reveal a significant increase in EVs of endothelial and platelet origin following short-term HTP inhalation with nicotine. Notably, no significant change was observed in leukocyte- and neutrophil-derived EVs. This increase in EVs suggests acute vascular stress, with peak levels observed 4 h post-exposure. The rise in endothelial and platelet-derived EVs aligns with documented responses to acute vascular injury, paralleling the effects seen with traditional cigarette and e-cigarette use. Despite HTPs being marketed as safer alternatives, our results indicate that nicotine-containing HTPs may still pose significant vascular risks. These findings contribute to the growing body of evidence cautioning against the perceived safety of HTPs and reinforce the importance of regulatory oversight and public health initiatives targeting nicotine delivery technologies. Trial Registrations: ClinicalTrials.gov ID: NCT04824495, registered 2021–01-07.

A novel strategy for discriminating genuine and adulterated marine oils is proposed. The strategy consists of i) determining the stereospecific distribution (sn-1, sn-2 and sn-3) of omega 3 polyunsaturated fatty acids (omega-3 PUFA) on the backbone of triacylglycerols by using liquid chromatography tandem mass spectrometry; ii) transforming the qualitative stereospecific information into quantitative data by means of a novel strategy; iii) analyzing the transformed data by principal component analysis. The proposed strategy was tested on pure oils (seal, salmon, cod liver, sandeel, blue whiting, herring), a mixture of blue whiting, herring, sandeel and Norway pout and some intentionally adulterated oils. In addition, some published krill oil data were analyzed to confirm the reliability of the new approach.

Background: Extreme weather is becoming more common due to climate change and threatens human health through climate-sensitive diseases, with very uneven effects around the globe. Low-income, rural populations in the Sahel region of west Africa are projected to be severely affected by climate change. Climate-sensitive disease burdens have been linked to weather conditions in areas of the Sahel, although comprehensive, disease-specific empirical evidence on these relationships is scarce. In this study, we aim to provide an analysis of the associations between weather conditions and cause-specific deaths over a 16-year period in Nouna, Burkina Faso.

Methods: In this longitudinal study, we used de-identified, daily cause-of-death data from the Health and Demographic Surveillance System led by the Centre de Recherche en Santé de Nouna (CRSN) in the National Institute of Public Health of Burkina Faso, to assess temporal associations between daily and weekly weather conditions (maximum temperature and total precipitation) and deaths attributed to specific climate-sensitive diseases. We implemented distributed-lag zero-inflated Poisson models for 13 disease-age groups at daily and weekly time lags. We included all deaths from climate-sensitive diseases in the CRSN demographic surveillance area from Jan 1, 2000 to Dec 31, 2015 in the analysis. We report the exposure–response relationships at percentiles representative of the exposure distributions of temperature and precipitation in the study area.

Findings: Of 8256 total deaths in the CRSN demographic surveillance area over the observation period, 6185 (74·9%) were caused by climate-sensitive diseases. Deaths from communicable diseases were most common. Heightened risk of death from all climate-sensitive communicable diseases, and malaria (both across all ages and in children younger than 5 years), was associated with 14-day lagged daily maximum temperatures at or above 41·1°C, the 90th percentile of daily maximum temperatures, compared with 36·4°C, the median (all communicable diseases: 41·9°C relative risk [RR] 1·38 [95% CI 1·08–1·77], 42·8°C 1·57 [1·13–2·18]; malaria all ages: 41·1°C 1·47 [1·05–2·05], 41·9°C 1·78 [1·21–2·61], 42·8°C 2·35 [1·37–4·03]; malaria younger than 5 years: 41·9°C 1·67 [1·02–2·73]). Heightened risk of death from communicable diseases was also associated with 14-day lagged total daily precipitation at or below 0·1 cm, the 49th percentile of total daily precipitation, compared with 1·4 cm, the median (all communicable diseases: 0·0 cm 1·04 [1·02–1·07], 0·1 cm 1·01 [1·006–1·02]; malaria all ages: 0·0 cm 1·04 [1·01–1·08], 0·1 cm 1·02 [1·00–1·03]; malaria younger than 5 years: 0·0 cm 1·05 [1·01–1·10], 0·1 cm 1·02 [1·00–1·04]). The only significant association with a non-communicable disease outcome was a heightened risk of death from climate-sensitive cardiovascular diseases in individuals aged 65 years and older associated with 7-day lagged daily maximum temperatures at or above 41·9°C (41·9°C 2·25 [1·06–4·81], 42·8°C 3·68 [1·46–9·25]). Over 8 cumulative weeks, we found that the risk of death from communicable diseases was heightened at all ages from temperatures at or above 41·1°C (41·1°C 1·23 [1·05–1·43], 41·9°C 1·30 [1·08–1·56], 42·8°C 1·35 [1·09–1·66]) and risk of death from malaria was heightened by precipitation at or above 45·3 cm (all ages: 45·3 cm 1·68 [1·31–2·14], 61·6 cm 1·72 [1·27–2·31], 87·7 cm 1·72 [1·16–2·55]; children younger than 5 years: 45·3 cm 1·81 [1·36–2·41], 61·6 cm 1·82 [1·29–2·56], 87·7 cm 1·93 [1·24–3·00]).

Interpretation: Our results indicate a high burden of death related to extreme weather in the Sahel region of west Africa. This burden is likely to increase with climate change. Climate preparedness programmes—such as extreme weather alerts, passive cooling architecture, and rainwater drainage—should be tested and implemented to prevent deaths from climate-sensitive diseases in vulnerable communities in Burkina Faso and the wider Sahel region. 

Background: The transmission of malaria and cholera depends on a great deal on climatic and environmental conditions, which are modulated by socioeconomic conditions, so understanding the influence of lagged climatic factors while adjusting for socioeconomic factors affecting malaria and cholera risk can aid in the timely implementation of interventions to reduce disease burden and adapt to changing climate. The aim of this thesis was to identify climatic and socio–demographic factors that influence malaria and cholera incidence in Mozambique, to develop and evaluate a climate-driven spatio–temporal malaria prediction model that could potentially be used in an early warning system, and to project future malaria incidence in Mozambique based on climate and socioeconomic projection scenarios.

Methods: Bayesian spatio–temporal models with integrated nested Laplace approximation (INLA) in combination with distributed lag nonlinear models (DLNMs) were used to assess the delayed and non-linear relationship between climatic and land use factors, on one hand, and malaria and cholera risk, on the other, while adjusting for socioeconomic conditions, spatio–temporal covariance, and seasonality. In addition, a spatio–temporal malaria prediction model was developed using lagged climatic covariates. The model’s ability to distinguish between high and low malaria seasons was evaluated using receiver operating characteristic (ROC) analysis. Future projection of malaria incidence to the end of twenty-first century in Mozambique was conducted based on a spatio–temporal Bayesian model, considering an ensemble of climate models in a multi-scenario approach.

Results: In papers I and IV, we identified the delayed and non-linear influence of climatic and land use factors on malaria and cholera risk. We found that malaria risk significantly increased at temperatures between 20 and 26°C and then dropped afterwards with a delay of more than four months. However, we found no significant influence of temperature on cholera risk. We observed that precipitation below 100 mm elevated malaria risk with a longer delay of up to five months, while malaria risk decreased with higher precipitation above 400 mm with a delay of just one month. For cholera, risk increased with precipitation above 200 mm with a delay of zero to two months. We found the highest malaria risk was associated with relative humidity (RH) of 55%, while RH above 70% decreased the risk. At RH values of 50–60%, malaria risk was elevated for shorter lags below two months. Similarly, RH of 54–67% increased cholera risk with a lag of three to five months. We found diverging influences of the Normalized Difference Vegetation Index (NDVI) on malaria and cholera risk. NDVI values above 0.2 were associated with high malaria risk with a delay of three months, while NDVI values below 0.2 were associated with elevated cholera risk with a delay of two to four months. We show that a high proportion of asset ownership (e.g., radios and mobile phones), a proxy for high social economic status, was associated with low malaria and cholera risk. We also show that toilet sharing increases cholera risk.

In Paper II, the selected spatio–temporal malaria prediction model included the non-linear functions of climate and NDVI variables with different lag combinations after adjusting for space and season, providing a lead time of up to four months. The model displayed high predictive accuracy with an R² of 0.8 between observed and predicted cases. The model’s ability to classify high and low malaria months was also high with an overall area under the curve (AUC) of 0.83.

In the third paper, we projected 21 million malaria cases, about a threefold (over 170%) increase by 2080, based on the SSP370 economic and emission scenario, relative to the baseline of 2018, when 7.7 million malaria cases were recorded. In the same period, mean temperatures in Mozambique are projected to increase by 3.6°C according to the SSP370 scenario.

Conclusion: In this thesis we employed advanced spatio–temporal Bayesian models to show that, when controlling for socioeconomic conditions, the lagged climate and land use factors impact malaria and cholera risk, following the biological mechanism of exposure before risk with some delay. We used the derived lag patterns to develop a spatio-temporal malaria prediction model with high skill, providing sufficient lead times up to four months, which could potentially be integrated into a malaria early warning system in Mozambique. Additionally, based on the developed prediction model, we show that climate change will triple the malaria burden in Mozambique in the future, so adequate actions to limit emissions should be taken. We show that combining climate services, disease surveillance, and advanced modelling can aid in adaptation to climate change.

The thesis contributes to key components of an early warning system, specifically on risk assessment and the use of surveillance data for predictive modeling, offering valuable guidance for malaria control initiatives in Mozambique and serving as a reference for low-resource settings.

Background: Temperature, precipitation, relative humidity (RH), and Normalized Different Vegetation Index (NDVI), influence malaria transmission dynamics. However, an understanding of interactions between socioeconomic indicators, environmental factors and malaria incidence can help design interventions to alleviate the high burden of malaria infections on vulnerable populations. Our study thus aimed to investigate the socioeconomic and climatological factors influencing spatial and temporal variability of malaria infections in Mozambique.

Methods: We used monthly malaria cases from 2016 to 2018 at the district level. We developed an hierarchical spatial–temporal model in a Bayesian framework. Monthly malaria cases were assumed to follow a negative binomial distribution. We used integrated nested Laplace approximation (INLA) in R for Bayesian inference and distributed lag nonlinear modeling (DLNM) framework to explore exposure-response relationships between climate variables and risk of malaria infection in Mozambique, while adjusting for socioeconomic factors.

Results: A total of 19,948,295 malaria cases were reported between 2016 and 2018 in Mozambique. Malaria risk increased with higher monthly mean temperatures between 20 and 29°C, at mean temperature of 25°C, the risk of malaria was 3.45 times higher (RR 3.45 [95%CI: 2.37–5.03]). Malaria risk was greatest for NDVI above 0.22. The risk of malaria was 1.34 times higher (1.34 [1.01–1.79]) at monthly RH of 55%. Malaria risk reduced by 26.1%, for total monthly precipitation of 480 mm (0.739 [95%CI: 0.61–0.90]) at lag 2 months, while for lower total monthly precipitation of 10 mm, the risk of malaria was 1.87 times higher (1.87 [1.30–2.69]). After adjusting for climate variables, having lower level of education significantly increased malaria risk (1.034 [1.014–1.054]) and having electricity (0.979 [0.967–0.992]) and sharing toilet facilities (0.957 [0.924–0.991]) significantly reduced malaria risk.

Conclusion: Our current study identified lag patterns and association between climate variables and malaria incidence in Mozambique. Extremes in climate variables were associated with an increased risk of malaria transmission, peaks in transmission were varied. Our findings provide insights for designing early warning, prevention, and control strategies to minimize seasonal malaria surges and associated infections in Mozambique a region where Malaria causes substantial burden from illness and deaths.

OBJECTIVES: This study aims to assess both socioeconomic and climatic factors of cholera morbidity in Mozambique considering both spatial and temporal dimensions.

DESIGN: An ecological longitudinal retrospective study using monthly provincial cholera cases from Mozambican Ministry of Health between 2000 and 2018. The cholera cases were linked to socioeconomic data from Mozambique Demographic and Health Surveys conducted in the period 2000-2018 and climatic data; relative humidity (RH), mean temperature, precipitation and Normalised Difference Vegetation Index (NDVI). A negative binomial regression model in a Bayesian framework was used to model cholera incidence while adjusting for the spatiotemporal covariance, lagged effect of environmental factors and the socioeconomic indicators.

SETTING: Eleven provinces in Mozambique.

RESULTS: Over the 19-year period, a total of 153 941 cholera cases were notified to the surveillance system in Mozambique. Risk of cholera increased with higher monthly mean temperatures above 24°C in comparison to the reference mean temperature of 23°C. At mean temperature of 19°C, cholera risk was higher at a lag of 5-6 months. At a shorter lag of 1 month, precipitation of 223.3 mm resulted in an 57% increase in cholera risk (relative risk, RR 1.57 (95% CI 1.06 to 2.31)). Cholera risk was greatest at 3 lag months with monthly NDVI of 0.137 (RR 1.220 (95% CI 1.042 to 1.430)), compared with the reference value of 0.2. At an RH of 54%, cholera RR was increased by 62% (RR 1.620 (95% CI 1.124 to 2.342)) at a lag of 4 months. We found that ownership of radio RR 0.29, (95% CI 0.109 to 0.776) and mobile phones RR 0.262 (95% CI 0.097 to 0.711) were significantly associated with low cholera risk.

CONCLUSION: The derived lagged patterns can provide appropriate lead times in a climate-driven cholera early warning system that could contribute to the prevention and management of outbreaks.

The occurrence of extreme rainfall events over mainland Mozambique associated with tropical cyclones (TC) Eline and Bonita is studied. Bonita caused catastrophic flooding in the central and some parts of northern Mozambique, thus forming the basis of the present study. Results show that the intensity of these TCs was maintained by the easterly wind from the Mascarene High. The northeasterly monsoon wind and northwesterlies from the Benguela current converged at the center of the TC, acting as a moisture source. The rainfall related to the two TCs befell in three stages and its magnitude attenuated progressively from the coastal region toward inland, concurring with the degeneration of the TCs. In stage one, for Eline, rainfall mainly concentrated in Tete, Manica, Niassa, North of Gaza provinces, the coastal Nampula, Zambezia, Sofala and Inhambane provinces. During Bonita’s inner-core circulation landfall, the northern and few parts of central Bonita were directly inundated. In the second stage, for Eline, the center of concentration of rainfall was in the central and southern parts of Mozambique. The mechanisms, including warm-air advection, vertical wind shear, could have contributed at the same time to the lifting vital for the generation of the storm during the second stage. The information herein is essential for future forecasting and monitoring of TC over the Indian Ocean. The findings form a good reference in the understanding of the recent cyclones, Kenneth and Idai that were destructive over Mozambique.

Background: There is strong experimental evidence that physiologic stress from high temperatures is greater if humidity is higher. However, heat indices developed to allow for this have not consistently predicted mortality better than dry-bulb temperature.

Objectives: We aimed to clarify the potential contribution of humidity an addition to temperature in predicting daily mortality in summer by using a large multicountry dataset.

Methods: In 445 cities in 24 countries, we fit a time-series regression model for summer mortality with a distributed lag nonlinear model (DLNM) for temperature (up to lag 3) and supplemented this with a range of terms for relative humidity (RH) and its interaction with temperature. City-specific associations were summarized using meta-analytic techniques.

Results: Adding a linear term for RH to the temperature term improved fit slightly, with an increase of 23% in RH (the 99th percentile anomaly) associated with a 1.1% [95% confidence interval (CI): 0.8, 1.3] decrease in mortality. Allowing curvature in the RH term or adding terms for interaction of RH with temperature did not improve the model fit. The humidity-related decreased risk was made up of a positive coefficient at lag 0 outweighed by negative coefficients at lags of 1–3 d. Key results were broadly robust to small model changes and replacing RH with absolute measures of humidity. Replacing temperature with apparent temperature, a metric combining humidity and temperature, reduced goodness of fit slightly.

Discussion:The absence of a positive association of humidity with mortality in summer in this large multinational study is counter to expectations from physiologic studies, though consistent with previous epidemiologic studies finding little evidence for improved prediction by heat indices. The result that there was a small negative average association of humidity with mortality should be interpreted cautiously; the lag structure has unclear interpretation and suggests the need for future work to clarify.

Background: Sick-leave rates are high due to stress-related illnesses, but little is still known about the process of recovery from these conditions. The aim of this study was to explore the experiences of the recovery process, 6 to 10 years after treatment in people previously diagnosed with exhaustion disorder (ED), focusing on facilitators and barriers for the process of recovery from ED, and recovery activities experienced as helpful during the recovery process.

Method: Thirty-eight participants (average age: 52 years, 32 females) previously diagnosed with ED were interviewed with semi-structured interviews 6–10 years after undergoing treatment. The interviews were analyzed with thematic analysis.

Results: Three themes resulted from the analysis. The first theme, “A long and rocky road”, summarizes the fluctuating path to feeling better and emphasizes barriers and facilitators that affected the process of recovery, with a focus on external life events and the participants’ own behaviors. Facilitators were changing workplace, receiving support, a reduction in stressors, and changed behaviors. Barriers were a poor work environment, caregiver responsibilities, negative life events and lack of support. The second theme “Recovery activities are needed every step of the way” describes how both the need for recovery activities and the types of activities experienced as helpful changed during the recovery process, from low-effort recovery activities for long periods of time to shorter and more active recovery activities. Recovery activities were described as important for self-care but hard to prioritize in everyday life. The last theme, “Reorienting to a new place”, captures the struggle to cope with the remaining impact of ED, and how internal facilitators in terms of understanding and acceptance were important to reorient and adjust to a new way of functioning.

Conclusions: Recovering from ED is a long and ongoing process where recovery activities are needed every step of the way. Our results highlight the importance of supporting personal recovery and long-term behavioral change, addressing individual stressors that may perpetuate the condition, and adjusting recovery activities according to where the person is in the recovery process.

Trial registration: ClinicalTrials.gov: NCT0073772. Registered on March 8, 2017. This study was pre-registered on Open Science Framework (osf.io).

A high turnover among principals may disrupt the continuity of leadership and negatively affect teachers and, by extension, the students. The aim was to investigate to what extent various work environment factors and signs of exhaustion were associated with reported intentions to change workplace among principals working in compulsory schools. A web-based questionnaire was administered twice, in 2018 and in 2019. Part I of the study involved cross-sectional analyses of the associations 2018 (n = 984) and 2019 (n = 884) between occupational factors, signs of exhaustion, and the intention to change workplace, using Generalized Estimating Equations models. Part II involved 631 principals who participated in both surveys. The patterns of intended and actual changes of workplace across two years were described, together with associated changes of occupational factors and signs of exhaustion. Supportive management was associated with an intention to stay, while demanding role conflicts and the feeling of being squeezed between management and co-workers (buffer-function) were associated with the intention to change workplace. The principals who intended to change their workplace reported more signs of exhaustion. To increase retention among principals, systematic efforts are probably needed at the national, municipal, and local level, in order to improve their working conditions.

Introduction: The prevalence of COPD tends to level off in populations with decreasing prevalence of smoking but the extent of underdiagnosis in such populations needs further investigation. Aim: To investigate underdiagnosis and misclassification of COPD with a focus on socio-economy, lifestyle determinants and healthcare utilization.

Method: The 1839 participants were selected from two ongoing large-scale epidemiological research programs: The Obstructive Lung Disease in Northern Sweden Studies and the West Sweden Asthma Study. COPDGOLD was defined according to the fixed post-bronchodilator spirometric criteria FEV1/FVC<0.70 in combination with respiratory symptoms.

Results: Among the 128 participants who fulfilled the criteria for COPDGOLD, the underdiagnosis was 83.6% (n = 107) of which 57.9% were men. The undiagnosed participants were younger, had higher FEV1% of predicted and less frequently a family history of bronchitis. One in four of the undiagnosed had utilized healthcare and had more frequently utilized healthcare due to a burden of respiratory symptoms than the general population without COPD. Underdiagnosis was not related to educational level. Misclassification of COPD was characterized by being a woman with low education, ever smoker, having respiratory symptoms and having a previous asthma diagnosis.

Conclusion: In the high income country Sweden, the underdiagnosis of COPD was highly prevalent. Reduced underdiagnosis can contribute to risk factor modification, medical treatment and self-management strategies in early stages of the disease, which may prevent disease progression and improve the quality of life among those affected. Therefore, there is a need to increase the use of spirometry in primary care to improve the diagnostic accuracy.

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 and 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.

The purpose of this study was to characterize different ethnic groups in Kyrgyzstan regarding cardiovascular disease (CVD) and mental distress, and to investigate the association between CVD and mental distress. The mental distress was measured in terms of sleep disturbance, burnout, and stress.

Materials and Methods: A cross-sectional study was carried out among six ethnic groups in Kyrgyzstan, aged 18 years and above. The sample was stratified for age, education, family status, and income. We used the Karolinska Sleep Questionnaire to assess sleep disturbance, the physical and emotional subscale of the Shirom Melamed Burnout Questionnaire to assess burnout, and the 10-item Perceived Stress Scale to assess perceived stress.

Results: The distribution of CVD differed significantly between the six ethnic groups, with higher prevalence among East Europeans, and Western Asians and lower among Other minorities and Central Asians. In all ethnic groups in Kyrgyzstan, individuals with CVD had increased odds of sleep disturbance and burnout. There was a significant difference in burnout and stress between persons with and without CVD in Kyrgyz and East European ethnic groups.

Conclusion: There was a significant difference in burnout and stress between persons with and without CVD in Kyrgyz and East European ethnic groups. In addition to CVD prevention, mitigating sleep disturbance and preventing burnout in the general population should be aimed at in public health measures.

INTRODUCTION: Air pollution is associated with increased risk of cardiovascular disease, possibly through chronic systemic inflammation that promotes the progression of atherosclerosis and the risk of cardiovascular events. This study aimed to investigate the associations between air pollution and established biomarkers of inflammation and cardiovascular disease.

METHODS: The Cardiovascular Subcohort of the Malmö Diet and Cancer cohort includes 6103 participants from the general population of Malmö, Sweden. The participants were recruited 1991-1994. Annual mean residential exposure to particulate matter < 2.5 and < 10 μm (PM_2.5 and PM₁₀), and nitrogen oxides (NO_x) at year of recruitment were assigned from dispersion models. Blood samples collected at recruitment, including blood cell counts, and biomarkers (lymphocyte- and neutrophil counts, C-reactive protein (CRP), soluble urokinase-type plasminogen activator receptor (suPAR), lipoprotein-associated phospholipase A2 (Lp-PLA₂), ceruloplasmin, orosomucoid, haptoglobin, complement-C3, and alpha-1-antitrypsin) were analyzed. Multiple linear regression models were used to investigate the cross-sectional associations between air pollutants and biomarkers.

RESULTS: The mean annual exposure levels in the cohort were only slightly or moderately above the new WHO guidelines of 5 μg/m³ PM_2.5 (10.5 μg/m³ PM_2.5). Residential PM_2.5 exposure was associated with increased levels of ceruloplasmin, orosomucoid, C3, alpha-1-antitrypsin, haptoglobin, Lp-PLA₂ and the neutrophil-lymphocyte ratio. Ceruloplasmin, orosomucoid, C3 and alpha-1-antitrypsin were also positively associated with PM₁₀. There were no associations between air pollutants and suPAR, leukocyte counts or CRP. The associations between particles and biomarkers were still significant after removing outliers and adjustment for CRP levels. The associations were more prominent in smokers.

CONCLUSION: Long-term residential exposure to moderate levels of particulate air pollution was associated with several biomarkers of inflammation and cardiovascular disease. This supports inflammation as a mechanism behind the association between air pollution and cardiovascular disease.

Air pollution is a major contributor to the global burden of disease and has been linked to several diseases and conditions, including cardiovascular disease. The biological mechanisms are related to inflammation and increased coagulability, factors that play an important role in the pathogenesis of venous thromboembolism (VTE, i.e., deep vein thrombosis or pulmonary embolism). This study investigates if long-term exposure to air pollution is associated with increased VTE incidence. The study followed 29 408 participants from the Malmö Diet and Cancer (MDC) cohort, which consists of adults aged 44–74 recruited in Malmö, Sweden between 1991 and 1996. For each participant, annual mean residential exposures to particulate matter <2.5 μg (PM_2.5) and <10 μg (PM₁₀), nitrogen oxides (NO_x) and black carbon (BC) from 1990 up to 2016 were calculated. Associations with VTE were analysed using Cox proportional hazard models for air pollution in the year of the VTE event (lag0) and the mean of the prior 1–10 years (lag1-10). Annual air pollution exposures for the full follow-up period had the following means: 10.8 μg/m³ for PM_2.5, 15.8 μg/m³ for PM₁₀, 27.7 μg/m³ for NO_x, and 0.96 μg/m³ for BC. The mean follow-up period was 19.5 years, with 1418 incident VTE events recorded during this period. Exposure to lag1-10 PM_2.5 was associated with an increased risk of VTE (HR 1.17 (95%CI 1.01–1.37)) per interquartile range (IQR) of 1.2 μg/m³ increase in PM_2.5 exposure. No significant associations were found between other pollutants or lag0 PM_2.5 and incident VTE. When VTE was divided into specific diagnoses, associations with lag1-10 PM_2.5 exposure were similarly positive for deep vein thrombosis but not for pulmonary embolism. Results persisted in sensitivity analyses and in multi-pollutant models. Long-term exposure to moderate concentrations of ambient PM_2.5 was associated with increased risks of VTE in the general population in Sweden.

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.