Low Concentration of Fecal Valeric Acid at 1 Year of Age Is Linked with Eczema and Food Allergy at 13 Years of Age: Findings from a Swedish Birth Cohort.

BACKGROUND: Short-chain fatty acids (SCFAs) are abundant bacterial metabolites in the gut, with immunomodulatory properties. Hence, they may influence allergy development. Previous studies have linked fecal SCFA pattern during infancy with allergy. However, the association of SCFAs to allergic outcomes in adolescence is not well established. Here, we examined how the fecal SCFA pattern at 1 year of age related to allergy at 13 years of age. METHODS: Levels of 8 SCFAs in fecal samples collected at 1 year of age from 110 children were quantified using gas chromatography. The same individuals were evaluated at 13 years of age for allergic symptoms, allergy diagnosis and allergy medication by questionnaire, and for sensitization using skin prick test against egg, milk, fish, wheat and soy, cat, dog, horse, birch, and timothy grass. RESULTS: The concentration of fecal valeric acid at 1 year of age was inversely associated with eczema at 13 years of age (OR 0.6, 95% CI: 0.4-1.0, p = 0.049) and showed a trend for inverse association with food allergy at 13 years of age (OR 0.6, 95% CI: 0.4-1.0, p = 0.057). In a sub-group analysis of children with eczema at 1 year of age, a higher concentration of fecal valeric acid was linked with reduced risk of their eczema remaining at 13 years of age (OR 0.2, 95% CI: 0.0-1.5), although this latter analysis did not reach statistical significance (p = 0.12). CONCLUSIONS: Our findings lend further support to the notion of early childhood as a critical period when allergy may be programmed via the gut microbiota. Higher levels of fecal valeric acid may be characteristic of a protective gut microbiota and/or actively contribute to protection from eczema and food allergy.

Prenatal and prepubertal exposures to tobacco smoke in men may cause lower lung function in future offspring: a three-generation study using a causal modelling approach.

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.

Being overweight in childhood, puberty, or early adulthood: Changing asthma risk in the next generation?

BACKGROUND: Overweight status and asthma have increased during the last decades. Being overweight is a known risk factor for asthma, but it is not known whether it might also increase asthma risk in the next generation. OBJECTIVE: We aimed to examine whether parents being overweight in childhood, adolescence, or adulthood is associated with asthma in their offspring. METHODS: We included 6347 adult offspring (age, 18-52 years) investigated in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) multigeneration study of 2044 fathers and 2549 mothers (age, 37-66 years) investigated in the European Community Respiratory Health Survey (ECRHS) study. Associations of parental overweight status at age 8 years, puberty, and age 30 years with offspring's childhood overweight status (potential mediator) and offspring's asthma with or without nasal allergies (outcomes) was analyzed by using 2-level logistic regression and 2-level multinomial logistic regression, respectively. Counterfactual-based mediation analysis was performed to establish whether observed associations were direct or indirect effects mediated through the offspring's own overweight status. RESULTS: We found statistically significant associations between both fathers' and mothers' childhood overweight status and offspring's childhood overweight status (odds ratio, 2.23 [95% CI, 1.45-3.42] and 2.45 [95% CI, 1.86-3.22], respectively). We also found a statistically significant effect of fathers' onset of being overweight in puberty on offspring's asthma without nasal allergies (relative risk ratio, 2.31 [95% CI, 1.23-4.33]). This effect was direct and not mediated through the offspring's own overweight status. No effect on offspring's asthma with nasal allergies was found. CONCLUSION: Our findings suggest that metabolic factors long before conception can increase asthma risk and that male puberty is a time window of particular importance for offspring's health.

Asthma and selective migration from farming environments in a three-generation cohort study.

Individuals raised on a farm appear to have less asthma than individual raised elsewhere. However, selective migration might contribute to this as may also the suggested protection from farm environment. This study investigated if parents with asthma are less likely to raise their children on a farm. This study involved three generations: 6045 participants in ECRHS/RHINE cohorts (born 1945-1973, denoted G1), their 10,121 parents (denoted G0) and their 8260 offspring participating in RHINESSA (born 1963-1998, denoted G2). G2-offspring provided information on parents not participating in ECRHS/RHINE. Asthma status and place of upbringing for all three generations were reported in questionnaires by G1 in 2010-2012 and by G2 in 2013-2016. Binary regressions with farm upbringing as outcome were performed to explore associations between parental asthma and offspring farm upbringing in G0-G1 and G1-G2. Having at least one parent with asthma was not associated with offspring farm upbringing, either in G1-G2 (RR 1.11, 95% CI 0.81-1.52) or in G0-G1 (RR 0.99, 0.85-1.15). G1 parents with asthma born in a city tended to move and raise their G2 offspring on a farm (RR 2.00, 1.12-3.55), while G1 parents with asthma born on a farm were less likely to raise their G2 offspring on a farm (RR 0.34, 0.11-1.06). This pattern was not observed in analyses of G0-G1. This study suggests that the protective effect from farm upbringing on subsequent asthma development could not be explained by selective migration. Intriguingly, asthmatic parents appeared to change environment when having children.

Agreement of offspring-reported parental smoking status: the RHINESSA generation study.

BACKGROUND: With increasing interest in exposure effects across generations, it is crucial to assess the validity of information given on behalf of others. AIMS: To compare adult's report of their parent's smoking status against parent's own report and examine predictors for discrepant answers. METHODS: We studied 7185 offspring (18-51 years) and one of their parents, n = 5307 (27-67 years) participating in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study. Information about parent's smoking status during offspring's childhood and mother's smoking status during pregnancy was obtained by questionnaires from parents and their offspring. We calculated sensitivity, specificity and Cohen's Kappa [κ] for agreement using parent's own report as the gold standard. We performed logistic regression to examine if offspring's sex, age, educational level, asthma status, own smoking status or parental status, as well as the parent's sex and amount of smoking during childhood predicted disagreement. RESULTS: The sensitivity for offspring's correct report of parent's smoking status during childhood (0-10 years) was 0.82 (95% CI 0.81-0.84), specificity was 0.95 (95% CI 0.95-0.96) and a good agreement was observed, κ = 0.79 (95% CI 0.78-0.80). Offspring's report of mothers' smoking status during pregnancy showed a lower sensitivity, 0.66 (95% CI 0.60-0.71), a slightly lower specificity, 0.92 (95% CI 0.90-0.95) and a good agreement, κ = 0.61 (95% CI 0.55-0.67). In multivariate logistic regression analysis, offspring not having children was a predictor for discrepant answers (odds ratio [OR] 2.11 [95% CI 1.21-3.69]). Low amount of parents' tobacco consumption, < 10 cigarettes/day (OR 2.72 [95% CI 1.71-4.31]) also predicted disagreement compared to ≥10 cigarettes per day, and so did offspring's reports of fathers' smoking status (OR 1.73 [95% CI 1.09-2.74]) compared to mothers' smoking status. Offspring's sex, asthma status, educational level, smoking status or age was not related to discrepant answers. CONCLUSIONS: Adults report their parent's smoking status during their childhood, as well as their mother' smoking status when pregnant with them, quite accurately. In the absence of parents' direct report, offspring's reports could be valuable.

Childhood asthma and smoking exposures before conception-A three-generational cohort study.

BACKGROUND: Some human and animal studies have recently shown that maternal grandmother's smoking during pregnancy increases the risk of asthma in the grandchildren. We have investigated whether sex of the exposed parent and/or grandchild modifies the association between grandmaternal smoking and grandchild asthma. METHODS: We formed a cohort study based on linkage of national registries with prospectively collected data over three generations. Smoking habits in early pregnancy were registered since 1982 and purchases of prescribed medication since 2005. In all, 10 329 children born since 2005 had information on maternal and grandmaternal smoking on both sides and were followed from birth up to 6 years of age. Ages when medication was purchased were used to classify the cohort into never, early transient (0-3 years), early persistent (0-3 and 4-6 years), and late-onset (4-6 years) phenotypes of childhood asthma. RESULTS: Maternal grandmother's smoking was associated with an increased odds of early persistent asthma after adjustment for maternal smoking and other confounders (odds ratio 1.29, 95% confidence interval 1.10-1.51). Grandchild sex did not modify the association. Paternal grandmother's smoking was not associated with any of the asthma phenotypes. CONCLUSION: Maternal but not paternal exposure to nicotine before conception was related to an increased risk of early persistent childhood asthma, but not other asthma phenotypes. Our findings are possibly consistent with a sex-specific mode of epigenetic transfer.

Agreement in reporting of asthma by parents or offspring - the RHINESSA generation study.

BACKGROUND: Self-report questionnaires are commonly used in epidemiology, but may be susceptible to misclassification, especially if answers are given on behalf of others, e.g. children or parents. The aim was to determine agreement and analyse predictors of disagreement in parents' reports of offspring asthma, and in offspring reports of parents' asthma. METHODS: In the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study, 6752 offspring (age range 18-51 years) and their parents (age range 39-66 years) reported their own and each other's asthma status. Agreement between asthma reports from offspring and parents was determined by calculating sensitivity, specificity, positive and negative predictive value and Cohen's kappa. The participants' own answers regarding themselves were defined as the gold standard. To investigate predictors for disagreement logistic regression analyses were performed to obtain odds ratios (OR) with 95% confidence intervals (CI) for sex, smoking status, education, comorbidity and severity of asthma. RESULTS: Agreement was good for parental report of offspring early onset asthma (< 10 years, Cohen's kappa 0.72) and moderate for offspring later onset asthma (Cohen's kappa 0.46). Specificity was 0.99 for both, and sensitivity was 0.68 and 0.36, respectively. For offspring report of maternal and paternal asthma the agreement was good (Cohen's kappa 0.69 and 0.68), specificity was 0.96 and 0.97, and sensitivity was 0.72 and 0.68, respectively. The positive predictive value (PPV) was lowest for offspring report of maternal asthma (0.75), and highest for parents' report of early onset asthma in the offspring (0.83). The negative predictive value (NPV) was high for all four groups (0.94-0.97). In multivariate analyses current smokers (OR = 1.46 [95% CI 1.05, 2.02]) and fathers (OR = 1.31 [95% CI 1.08, 1.59]) were more likely to report offspring asthma incorrectly. Offspring wheeze was associated with reporting parental asthma incorrectly (OR = 1.60 [95% CI 1.21, 2.11]), both under- and over reporting. CONCLUSIONS: Asthma reports across generations show moderate to good agreement, making information from other generations a useful tool in the absence of direct reports.

Validation of self-reported figural drawing scales against anthropometric measurements in adults.

OBJECTIVE: The aim of the present study was to validate figural drawing scales depicting extremely lean to extremely obese subjects to obtain proxies for BMI and waist circumference in postal surveys. DESIGN: Reported figural scales and anthropometric data from a large population-based postal survey were validated with measured anthropometric data from the same individuals by means of receiver-operating characteristic curves and a BMI prediction model. SETTING: Adult participants in a Scandinavian cohort study first recruited in 1990 and followed up twice since. SUBJECTS: Individuals aged 38-66 years with complete data for BMI (n 1580) and waist circumference (n 1017). RESULTS: Median BMI and waist circumference increased exponentially with increasing figural scales. Receiver-operating characteristic curve analyses showed a high predictive ability to identify individuals with BMI > 25·0 kg/m2 in both sexes. The optimal figural scales for identifying overweight or obese individuals with a correct detection rate were 4 and 5 in women, and 5 and 6 in men, respectively. The prediction model explained 74 % of the variance among women and 62 % among men. Predicted BMI differed only marginally from objectively measured BMI. CONCLUSIONS: Figural drawing scales explained a large part of the anthropometric variance in this population and showed a high predictive ability for identifying overweight/obese subjects. These figural scales can be used with confidence as proxies of BMI and waist circumference in settings where objective measures are not feasible.

A rapid growth rate in early childhood is a risk factor for becoming overweight in late adolescence.

AIM: We evaluated whether body mass index (BMI) and rapid growth in early life were associated with an increased risk of becoming overweight at 16 and 18 years of age. METHODS: The study population comprised all children born in Sweden on the 15th of each month in 1981. Individuals born on the 5th, 10th and 20th of every month were added for counties with low population densities. Information on weight and height was collected from birth up to 18 years of age for 98.6% of the 3537 children identified. RESULTS: Weight at 12 months of age was associated with being overweight at both 16 and 18 years of age. Rapid weight gain from birth to 12 months was associated with higher odds for being overweight later in life, and the weight gain between 18 months and four years of age was the strongest risk factor for being overweight in late adolescence in both sexes. There was no association between a birthweight of <2500 g or >4500 g and being overweight at 16 or 18 years of age. CONCLUSION: Fast growth during early childhood was associated with an increased risk of being overweight later in life, emphasising the importance of early prevention.

Place of upbringing in early childhood as related to inflammatory bowel diseases in adulthood: a population-based cohort study in Northern Europe.

BACKGROUND: The two inflammatory bowel diseases (IBD), ulcerative colitis and Crohn's disease, has increased rapidly during the twentieth century, but the aetiology is still poorly understood. Impaired immunological competence due to decreasing biodiversity and altered microbial stimulation is a suggested explanation. OBJECTIVE: Place of upbringing was used as a proxy for the level and diversity of microbial stimulation to investigate the effects on the prevalence of IBD in adulthood. METHODS: Respiratory Health in Northern Europe (RHINE) III is a postal follow-up questionnaire of the European Community Respiratory Health Survey (ECRHS) cohorts established in 1989-1992. The study population was 10,864 subjects born 1945-1971 in Denmark, Norway, Sweden, Iceland and Estonia, who responded to questionnaires in 2000-2002 and 2010-2012. Data were analysed in logistic and Cox regression models taking age, sex, smoking and body mass index into consideration. RESULTS: Being born and raised on a livestock farm the first 5 years of life was associated with a lower risk of IBD compared to city living in logistic (OR 0.54, 95 % CI 0.31; 0.94) and Cox regression models (HR 0.55, 95 % CI 0.31; 0.98). Random-effect meta-analysis did not identify geographical difference in this association. Furthermore, there was a significant trend comparing livestock farm living, village and city living (p < 0.01). Sub-analyses showed that the protective effect was only present among subjects born after 1952 (OR 0.25, 95 % CI 0.11; 0.61). CONCLUSION: This study suggests a protective effect from livestock farm living in early childhood on the occurrence of IBD in adulthood, however only among subjects born after 1952. We speculate that lower microbial diversity is an explanation for the findings.

An expert assessment on climate change and health - with a European focus on lungs and allergies.

BACKGROUND: For almost 20 years, the Intergovernmental Panel on Climate Change has been assessing the potential health risks associated with climate change; with increasingly convincing evidence that climate change presents existing impacts on human health. In industrialized countries climate change may further affect public health and in particular respiratory health, through existing health stressors, including, anticipated increased number of deaths and acute morbidity due to heat waves; increased frequency of cardiopulmonary events due to higher concentrations of air pollutants; and altered spatial and temporal distribution of allergens and some infectious disease vectors. Additionally exposure to moulds and contaminants from water damaged buildings may increase. METHODS: We undertook an expert elicitation amongst European researchers engaged in environmental medicine or respiratory health. All experts were actively publishing researchers on lung disease and air pollution, climate and health or a closely related research. We conducted an online questionnaire on proposed causal diagrams and determined levels of confidence that climate change will have an impact on a series of stressors. In a workshop following the online questionnaire, half of the experts further discussed the results and reasons for differences in assessments of the state of knowledge on exposures and health effects. RESULTS: Out of 16 experts, 100% expressed high to very high confidence that climate change would increase the frequency of heat waves. At least half expressed high or very high confidence that climate change would increase levels of pollen (50%), particulate matter (PM2.5) (55%), and ozone (70%). While clarity is needed around the impacts of increased exposures to health impacts of some stressors, including ozone and particulate matter levels, it was noted that definitive knowledge is not a prerequisite for policy action. Information to the public, preventive measures, monitoring and warning systems were among the most commonly mentioned preventative actions. CONCLUSIONS: This group of experts identifies clear health risks associated with climate change, and express opinions about these risks even while they do not necessarily regard themselves as covering all areas of expertise. Since some changes in exposure have already been observed, the consensus is that there is already a scientific basis for preventative action, and that the associated adaptation and mitigation policies should also be evidence based.

Pollen exposure in pregnancy and infancy and risk of asthma hospitalisation - a register based cohort study.

BACKGROUND: A seasonal effect of month of birth and risk of allergic disease has been suggested by numerous studies. Few studies have directly measured pollen exposures at different points during pregnancy and in early life, and assessed their effects on risk of respiratory disease outcomes. METHODS: Pollen exposure was calculated for the first and last 12 weeks of pregnancy and the first 12 weeks of infancy for all children conceived by women residing in Stockholm, Sweden, between 1988 and 1995. Hospital admission data for respiratory conditions in the first year of life was also collected. RESULTS: Out of 110,381 children, 940 had been hospitalised for asthma by 12-months of age. Pollen levels showed both marked seasonal variations and between year differences. Exposure to high levels of pollen in the last 12 weeks of pregnancy was associated with an increased risk of asthma hospitalisation (aOR = 1.35, 95% CI = 1.07-1.71 for highest quartile versus remaining infants). Exposure to high levels of pollen in the first three months of life was associated with a reduced risk (aOR = 0.76, 95% CI = 0.59-0.98) but only in children of heavy smoking mothers. CONCLUSIONS: High levels of pollen exposure during late pregnancy were somewhat unexpectedly associated with an elevated risk of hospitalisation for asthma within the first year of life.

Cohort profile: the multigeneration Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) cohort.

PURPOSE: The Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) cohort was established to (1) investigate how exposures before conception and in previous generations influence health and disease, particularly allergies and respiratory health, (2) identify susceptible time windows and (3) explore underlying mechanisms. The ultimate aim is to facilitate efficient intervention strategies targeting multiple generations. PARTICIPANTS: RHINESSA includes study participants of multiple generations from ten study centres in Norway (1), Denmark (1), Sweden (3), Iceland (1), Estonia (1), Spain (2) and Australia (1). The RHINESSA core cohort, adult offspring generation 3 (G3), was first investigated in 2014-17 in a questionnaire study (N=8818, age 18-53 years) and a clinical study (subsample, n=1405). Their G2 parents participated in the population-based cohorts, European Community Respiratory Heath Survey and Respiratory Health In Northern Europe, followed since the early 1990s when they were 20-44 years old, at 8-10 years intervals. Study protocols are harmonised across generations. FINDINGS TO DATE: Collected data include spirometry, skin prick tests, exhaled nitric oxide, anthropometrics, bioimpedance, blood pressure; questionnaire/interview data on respiratory/general/reproductive health, indoor/outdoor environment, smoking, occupation, general characteristics and lifestyle; biobanked blood, urine, gingival fluid, skin swabs; measured specific and total IgE, DNA methylation, sex hormones and oral microbiome. Research results suggest that parental environment years before conception, in particular, father's exposures such as smoking and overweight, may be of key importance for asthma and lung function, and that there is an important susceptibility window in male prepuberty. Statistical analyses developed to approach causal inference suggest that these associations may be causal. DNA methylation studies suggest a mechanism for transfer of father's exposures to offspring health and disease through impact on offspring DNA methylation. FUTURE PLANS: Follow-up is planned at 5-8 years intervals, first in 2021-2023. Linkage with health registries contributes to follow-up of the cohort.

Parental Prepuberty Overweight and Offspring Lung Function.

In a recent study we found that fathers' but not mothers' onset of overweight in puberty was associated with asthma in adult offspring. The potential impact on offspring's adult lung function, a key marker of general and respiratory health, has not been studied. We investigated the potential causal effects of parents' overweight on adult offspring's lung function within the paternal and maternal lines. We included 929 offspring (aged 18-54, 54% daughters) of 308 fathers and 388 mothers (aged 40-66). Counterfactual-based multi-group mediation analyses by offspring's sex (potential moderator) were used, with offspring's prepubertal overweight and/or adult height as potential mediators. Unknown confounding was addressed by simulation analyses. Fathers' overweight before puberty had a negative indirect effect, mediated through sons' height, on sons' forced expiratory volume in one second (FEV1) (beta (95% CI): -144 (-272, -23) mL) and forced vital capacity (FVC) (beta (95% CI): -210 (-380, -34) mL), and a negative direct effect on sons' FVC (beta (95% CI): -262 (-501, -9) mL); statistically significant effects on FEV1/FVC were not observed. Mothers' overweight before puberty had neither direct nor indirect effects on offspring's lung function. Fathers' overweight starting before puberty appears to cause lower FEV1 and FVC in their future sons. The effects were partly mediated through sons' adult height but not through sons' prepubertal overweight.

High salivary secretory IgA antibody levels are associated with less late-onset wheezing in IgE-sensitized infants.

Low levels of secretory IgA (SIgA) and transient IgA deficiency have been associated with an increased risk for allergy, but data are conflicting. The aim was to assess the relationship between salivary SIgA antibody levels at 1 yr and wheezing at age four in a birth cohort, in particular the possible protective role of salivary SIgA in sensitized children. Saliva samples were obtained from all children (n=67) with a positive skin prick test (SPT) at 1 yr and 212 children with a negative SPT. In all, 200 of these children responded to questionnaires at 4 yrs and 183 were skin prick tested at that age. The levels of salivary SIgA and salivary IgA antibodies to the most common food allergen egg and inhalant allergen cat were analyzed by ELISA. Serum was analyzed for IgE antibodies to egg and cat. Development of late-onset wheezing was associated with low SIgA levels in children with positive SPT to at least one allergen both at 1 and 4 yrs of age (p=0.04), as well as in children with circulating IgE antibodies to egg or cat at 1 yr (p=0.02). None of nine persistently sensitized children with SIgA levels in the upper quartile developed wheezing, when compared to 10/20 children with lower levels (p=0.01). Older siblings, more than three infections during infancy, at least one smoking parent, and male gender, were all associated with SIgA in the upper quartile. In conclusion, high levels of SIgA antibodies in sensitized infants were associated with significantly less late-onset wheezing, supporting a protective role against development of asthmatic symptoms. Recurrent infections and other factors supporting an increased microbial pressure during infancy were associated with high levels of salivary SIgA.

Early childhood exposure to ambient air pollution is associated with increased risk of paediatric asthma: An administrative cohort study from Stockholm, Sweden.

INTRODUCTION: Asthma is a complex, heterogeneous disease and one of the most common chronic diseases among children. Exposure to ambient air pollution in early life and childhood may influence asthma aetiology, but it is uncertain which specific components of air pollution and exposure windows are of importance. The role of socio-economic status (SES) is also unclear. The aims of the present study are, therefore, to investigate how various exposure windows of different pollutants affect risk-induced asthma in early life and to explore the possible effect SES has on that relationship. METHODS: The study population was constructed using register data on all singleton births in the greater Stockholm area between 2006 and 2013. Exposure to ambient black carbon (BC), fine particulate matter (PM2.5), primary organic carbon (pOC) secondary organic aerosols (SOA), secondary inorganic aerosols, and oxidative potential at the residential address was modelled as mean values for the entire pregnancy period, the first year of life and the first three years of life. Swedish national registers were used to define the outcome: asthma diagnosis assessed at hospital during the first six years of life. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were modelled with Cox proportional hazards model with age as the underlying time-scale, adjusting for relevant potential confounding variables. RESULTS: An increased risk for developing childhood asthma was observed in association with exposure to PM2.5, pOC and SOA during the first three years of life. With an interquartile range increase in exposure, the HRs were 1.06 (95% CI: 1.01-1.10), 1.05 (95% CI: 1.02-1.09) and 1.02 (95% CI: 1.00-1.04), for PM2.5, pOC and SOA, respectively, in the fully adjusted models. Exposure during foetal life or the first year of life was not associated with asthma risk, and the other pollutants were not statistically significantly associated with increased risk. Furthermore, the increase in risk associated with PM2.5 and the components BC, pOC and SOA were stronger in areas with lower SES. CONCLUSION: Our results suggest that exposure to air pollution during the first three years of life may increase the risk for asthma in early childhood. The findings further imply a possible increased vulnerability to air pollution-attributed asthma among low SES children.

Does parental farm upbringing influence the risk of asthma in offspring? A three-generation study.

BACKGROUND: A farm upbringing has been associated with lower risk of asthma and methylation of asthma-related genes. As such, a farm upbringing has the potential to transfer asthma risk across generations, but this has never been investigated. We aimed to study the generational effects from a parental farm upbringing on offspring asthma. METHODS: Our study involved three generations: 5759 participants from the European Community Respiratory Health Survey (ECRHS) study (born 1945-1971, denoted G1), their 9991 parents (G0) and their 8260 offspring (G2) participating in RHINESSA (Respiratory Health In Northern Europe, Spain and Australia). Questionnaire data were collected on G0 and G1 from G1 in 2010 and on G2 from themselves in 2013. The parental/grandparental place of upbringing was categorized: (i) both parents from farm; (ii) mother from farm, father from village/city; (iii) father from farm, mother from village/city; (iv) both parents from village or one parent from village and one from city; (v) both parents from city (reference group). Grandparental upbringing was equivalently categorized. Offspring asthma was self-reported and data were analysed using Cox-regression models with G2 age as the time scale. RESULTS: A parental farm upbringing was not associated with offspring asthma when compared with city upbringing [hazard ratio (HR) 1.12, 95% confidence interval (CI) 0.74-1.69]. Findings remained similar when stratified by offspring upbringing and asthma phenotypes. Quantitative bias analyses showed similar estimates for alternative data sources. A grandparental farm upbringing was not associated with offspring asthma in either the maternal (HR 1.05, 95% CI 0.67-1.65) or paternal line (HR 1.02, 95% CI 0.62-1.68). CONCLUSIONS: This multigenerational analysis suggests no evidence of an association between parental/grandparental farm upbringing and offspring asthma.

Lifelong exposure to air pollution and greenness in relation to asthma, rhinitis and lung function in adulthood.

OBJECTIVES: To investigate if air pollution and greenness exposure from birth till adulthood affects adult asthma, rhinitis and lung function. METHODS: We analysed data from 3428 participants (mean age 28) in the RHINESSA study in Norway and Sweden. Individual mean annual residential exposures to nitrogen dioxide (NO2), particulate matter (PM10 and PM2.5), black carbon (BC), ozone (O3) and greenness (normalized difference vegetation index (NDVI)) were averaged across susceptibility windows (0-10 years, 10-18 years, lifetime, adulthood (year before study participation)) and analysed in relation to physician diagnosed asthma (ever/allergic/non-allergic), asthma attack last 12 months, current rhinitis and low lung function (lower limit of normal (LLN), z-scores of forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC below 1.64). We performed logistic regression for asthma attack, rhinitis and LLN lung function (clustered with family and study centre), and conditional logistic regression with a matched case-control design for ever/allergic/non-allergic asthma. Multivariable models were adjusted for parental asthma and education. RESULTS: Childhood, adolescence and adult exposure to NO2, PM10 and O3 were associated with an increased risk of asthma attacks (ORs between 1.29 and 2.25), but not with physician diagnosed asthma. For rhinitis, adulthood exposures seemed to be most important. Childhood and adolescence exposures to PM2.5 and O3 were associated with lower lung function, in particular FEV1 (range ORs 2.65 to 4.21). No associations between NDVI and asthma or rhinitis were revealed, but increased NDVI was associated with lower FEV1 and FVC in all susceptibility windows (range ORs 1.39 to 1.74). CONCLUSIONS: Air pollution exposures in childhood, adolescence and adulthood were associated with increased risk of asthma attacks, rhinitis and low lung function in adulthood. Greenness was not associated with asthma or rhinitis, but was a risk factor for low lung function.