Grandmaternal smoking increases asthma risk in grandchildren: A nationwide Swedish cohort.

BACKGROUND: There is growing interest in exposures prior to conception as possible risk factors for offspring asthma. Although partially supported by evidence from limited human studies, current evidence is inconsistent and based on recall of exposure status. OBJECTIVE: We aimed to investigate grandmaternal smoking during pregnancy and the risk of asthma in grandchildren using prospectively collected population-based data. METHODS: Information on grandmaternal and maternal smoking during pregnancy and grandchild use of asthma medications was collected from national Swedish registries. Associations between grandmaternal smoking during pregnancy (10-12 weeks) and asthma medication use in grandchildren were investigated using generalized estimating equations. Ages at which asthma medications were prescribed classified childhood asthma into never, early transient (0-3 years), late onset (3-6 years) and early persistent (0-3 and 3-6 years) phenotypes. RESULTS: From 1982 to 1986, 44 583 grandmothers gave birth to 46 197 mothers, who gave birth to 66 271 grandchildren (born 1996-2010). Children aged 1-6 years had an increased asthma risk if their grandmothers had smoked during pregnancy, with a higher risk for more exposure (10+ cigs/d; adjusted OR 1.23; 1.17, 1.30). Maternal smoking did not modify this relationship. CONCLUSIONS & CLINICAL RELEVANCE: Children had an increased risk of asthma in the first 6 years of life if their grandmothers smoked during early pregnancy, independent of maternal smoking. Importantly, this exhibited a dose-response relationship and was associated with a persistent childhood asthma phenotype. These findings support possible epigenetic transmission of risk from environmental exposures in previous generations.

Association between the age of solid food introduction and eczema: A systematic review and a meta-analysis.

INTRODUCTION: Eczema is a common childhood ailment responsible for a considerable disease burden. Both timing of introduction to solid food and allergenic food are believed to be related to childhood eczema. Despite the growing body of evidence, the relationship between timing of any solid food introduction (allergenic and/or non-allergenic) and development of eczema has not previously been systematically reviewed. METHODS: PubMed and EMBASE databases were searched using food and eczema terms. Two authors selected papers according to the inclusion criteria and extracted information on study characteristics and measures of association. Meta-analyses were performed after grouping studies according to the age and type of exposure. RESULTS: A total of 17 papers met the inclusion criteria, reporting results from 16 study populations. Of these, 11 were cohort studies, 2 case-controls, 1 cross-sectional study and 2 randomized controlled trials. Limited meta-analyses were performed due to heterogeneity between studies. Timing of solid food introduction was not associated with eczema. One randomized controlled trial provided weak evidence of an association between early allergenic (around 4 months) food introduction and reduced risk of eczema. CONCLUSIONS: The available evidence is currently insufficient to determine whether the timing of introduction of any solid food influences the risk of eczema.

Association of breast milk fatty acids with allergic disease outcomes-A systematic review.

INTRODUCTION: Dietary polyunsaturated fatty acids (PUFAs) have immunoregulatory properties. Breast milk is rich in PUFA, and it has been hypothesized that these PUFAs may be important in the aetiology of allergic diseases. Despite a growing body of evidence, the associations between breast milk PUFA and allergic disease have not previously been systematically reviewed. METHODS: The search was performed in PubMed and EMBASE databases using breastfeeding, fatty acid and allergic disease terms. Two authors were involved in selecting papers for review according to the inclusion criteria and extracting information on study characteristics and measures of association. Only studies that reported numeric associations between concentration of breast milk fatty acids and allergic disease outcomes were included. RESULTS: A total of 18 papers met the inclusion criteria, reporting results from 15 study populations. The majority were cohort studies (n=11), with data from only two case-control and two cross-sectional studies. Sample size varied between 30 and 352 participants, and follow-up time of the cohorts varied between 3 months and 14 years. Nine studies reported on eczema, seven reported on sensitization, and only five reported on asthma/wheeze. There was heterogeneity among studies in terms of presenting the association between PUFA and allergy; therefore, estimates could not be pooled. Only a few studies observed associations between n-3 and n-6 PUFAs and allergic disease, and the magnitude of this effect varied greatly. CONCLUSIONS: There is insufficient evidence to suggest that colostrum or breast milk polyunsaturated fatty acids influence the risk of childhood allergic diseases.

The effects of growing up on a farm on adult lung function and allergic phenotypes: an international population-based study.

RATIONALE: Evidence has suggested that exposure to environmental or microbial biodiversity in early life may impact subsequent lung function and allergic disease risk. OBJECTIVES: To investigate the influence of childhood living environment and biodiversity indicators on atopy, asthma and lung function in adulthood. METHODS AND MEASUREMENTS: The European Community Respiratory Health Survey II investigated ∼10 201 participants aged 26-54 years from 14 countries, including participants' place of upbringing (farm, rural environment or inner city) before age 5 years. A 'biodiversity score' was created based on childhood exposure to cats, dogs, day care, bedroom sharing and older siblings. Associations with lung function, bronchial hyper-responsiveness (BHR), allergic sensitisation, asthma and rhinitis were analysed. MAIN RESULTS: As compared with a city upbringing, those with early-life farm exposure had less atopic sensitisation (adjusted OR 0.46, 95% CI 0.37 to 0.58), atopic BHR (0.54 (0.35 to 0.83)), atopic asthma (0.47 (0.28 to 0.81)) and atopic rhinitis (0.43 (0.32 to 0.57)), but not non-atopic outcomes. Less pronounced protective effects were observed for rural environment exposures. Women with a farm upbringing had higher FEV1 (adjusted difference 110 mL (64 to 157)), independent of sensitisation and asthma. In an inner city environment, a higher biodiversity score was related to less allergic sensitisation. CONCLUSIONS: This is the first study to report beneficial effects of growing up on a farm on adult FEV1. Our study confirmed the beneficial effects of early farm life on sensitisation, asthma and rhinitis, and found a similar association for BHR. In persons with an urban upbringing, a higher biodiversity score predicted less allergic sensitisation, but to a lesser magnitude than a childhood farm environment.

Breast milk polyunsaturated fatty acids: associations with adolescent allergic disease and lung function.

BACKGROUND: It has been hypothesized that n-3 PUFA in breast milk may assist immune and lung development. There are very limited data on possible long-term effects on allergic disease and lung function. The aim was to investigate associations of n-3 and n-6 PUFA levels in colostrum and breast milk with allergic disease and lung function at ages 12 and 18 years. METHODS: Polyunsaturated fatty acids were measured in 194 colostrum samples and in 118 three-month expressed breast milk samples from mothers of children enrolled in the Melbourne Atopy Cohort (MACS) Study, a high-risk birth cohort study. Associations with allergic diseases, skin prick tests and lung function assessed at 12 and 18 years were estimated using multivariable regression. RESULTS: Higher levels of n-3 but not n-6 PUFAs in colostrum were associated with a trend towards increased odds of allergic diseases, with strong associations observed for allergic rhinitis at 12 (OR = 5.69[95% CI: 1.83,17.60] per weight%) and 18 years (4.43[1.46,13.39]) and eczema at 18 years (9.89[1.44, 68.49]). Higher levels of colostrum n-3 PUFAs were associated with reduced sensitization (3.37[1.18, 9.6]), mean FEV1 (-166 ml [-332, -1]) and FEV1 /FVC ratio (-4.6%, [-8.1, -1.1]) at 12 years. CONCLUSION: Higher levels of colostrum n-3 PUFAs were associated with increased risks of allergic rhinitis and eczema up to 18 years, and sensitization and reduced lung function at 12 years. As residual confounding may have caused these associations, they should be replicated, but these results could indicate that strategies that increase maternal n-3 PUFA intake may not aid in allergic disease prevention.

The skin barrier function gene SPINK5 is associated with challenge-proven IgE-mediated food allergy in infants.

BACKGROUND: A defective skin barrier is hypothesized to be an important route of sensitization to dietary antigens and may lead to food allergy in some children. Missense mutations in the serine peptidase inhibitor Kazal type 5 (SPINK5) skin barrier gene have previously been associated with allergic conditions. OBJECTIVE: To determine whether genetic variants in and around SPINK5 are associated with IgE-mediated food allergy. METHOD: We genotyped 71 "tag" single nucleotide polymorphisms (tag-SNPs) within a region spanning ~263 kb including SPINK5 (~61 kb) in n=722 (n=367 food-allergic, n=199 food-sensitized-tolerant and n=156 non-food-allergic controls) 12-month-old infants (discovery sample) phenotyped for food allergy with the gold standard oral food challenge. Transepidermal water loss (TEWL) measures were collected at 12 months from a subset (n=150) of these individuals. SNPs were tested for association with food allergy using the Cochran-Mantel-Haenszel test adjusting for ancestry strata. Association analyses were replicated in an independent sample group derived from four paediatric cohorts, total n=533 (n=203 food-allergic, n=330 non-food-allergic), mean age 2.5 years, with food allergy defined by either clinical history of reactivity, 95% positive predictive value (PPV) or challenge, corrected for ancestry by principal components. RESULTS: SPINK5 variant rs9325071 (A⟶G) was associated with challenge-proven food allergy in the discovery sample (P=.001, OR=2.95, CI=1.49-5.83). This association was further supported by replication (P=.007, OR=1.58, CI=1.13-2.20) and by meta-analysis (P=.0004, OR=1.65). Variant rs9325071 is associated with decreased SPINK5 gene expression in the skin in publicly available genotype-tissue expression data, and we generated preliminary evidence for association of this SNP with elevated TEWL also. CONCLUSIONS: We report, for the first time, association between SPINK5 variant rs9325071 and challenge-proven IgE-mediated food allergy.

Residential greenness and allergic respiratory diseases in children and adolescents - A systematic review and meta-analysis.

BACKGROUND: The aetiology of allergic respiratory disease in children is not yet fully understood. Environmental factors are believed to play a major part. The amount of green vegetation surrounding the home (residential greenness) has been recently identified as a potentially important exposure OBJECTIVES: Our goal was to provide a systematic review and quantitative summary of the evidence regarding the relationship between residential greenness and allergic respiratory diseases in children. METHODS: Peer-reviewed literature published prior to 1 March 2017 was systematically searched using nine electronic databases. Meta-analyses were conducted if at least three studies published risk estimates for the same outcome and exposure measures. RESULTS: We included 11 articles across broad outcomes of asthma and allergic rhinitis. Reported effects were inconsistent with varying measures to define residential greenness. Only limited meta-analysis could be conducted, with the pooled odds ratios for asthma (OR 1.01 95%CI 0.93, 1.09; I2 68.1%) and allergic rhinitis (OR 0.99 95%CI 0.87, 1.12; I2 72.9%) being significantly heterogeneous. CONCLUSIONS: Inconsistencies between the studies were too large to accurately assess the association between residential greenness and allergic respiratory disease. A standardised global measure of greenness which accounts for seasonal variation at a specific relevant buffer size is needed to create a more cohesive body of evidence and for future examination of the effect of residential greenness on allergic respiratory diseases.

Pre-natal and post-natal exposure to pet ownership and lung function in children: The Seven Northeastern Cities Study.

To evaluate the association between pre-natal and post-natal exposure to pet ownership and lung function in children, a cross-sectional study named Seven Northeastern Cities (SNEC) study was conducted. In this study, children's lung function including the forced expiratory volume in 1 second (FEV1 ), forced vital capacity (FVC), maximal mid-expiratory flow (MMEF), and peak expiratory flow (PEF) were measured by spirometers, and pet ownership situations were collected by questionnaire. Analyzed by multiple logistic regression and generalized linear modeling, we found that for all subjects, pet exposure in the first 2 years of life was significantly associated with lung function impairment of FVC<85% predicted (adjusted odds ratio [aOR]=1.28; 95% confidence interval [CI]: 1.01, 1.63). For current pet exposure, the increased odds of lung function impairment ranged from 35% (aOR=1.35; 95%CI: 1.12, 1.62) for FVC<85% predicted to 57% (aOR=1.57; 95%CI: 1.29, 1.93) for FEV1 <85% predicted. The in utero exposure was not related to lung function impairment. Compared with other pets, higher odds were observed among children with dogs. When stratified by gender, girls with current pet exposure were more likely to have lung function impairment than boys. It implies self-reported exposures to pets were negatively associated with lung function among the children under study.

The march from early life food sensitization to allergic disease: a systematic review and meta-analyses of birth cohort studies.

BACKGROUND: There is growing evidence for an increase in food allergies. The question of whether early life food sensitization, a primary step in food allergies, leads to other allergic disease is a controversial but important issue. Birth cohorts are an ideal design to answer this question. OBJECTIVES: We aimed to systematically investigate and meta-analyse the evidence for associations between early food sensitization and allergic disease in birth cohorts. METHODS: MEDLINE and SCOPUS databases were searched for birth cohorts that have investigated the association between food sensitization in the first 2 years and subsequent wheeze/asthma, eczema and/or allergic rhinitis. We performed meta-analyses using random-effects models to obtain pooled estimates, stratified by age group. RESULTS: The search yielded fifteen original articles representing thirteen cohorts. Early life food sensitization was associated with an increased risk of infantile eczema, childhood wheeze/asthma, eczema and allergic rhinitis and young adult asthma. Meta-analyses demonstrated that early life food sensitization is related to an increased risk of wheeze/asthma (pooled OR 2.9; 95% CI 2.0-4.0), eczema (pooled OR 2.7; 95% CI 1.7-4.4) and allergic rhinitis (pooled OR 3.1; 95% CI 1.9-4.9) from 4 to 8 years. CONCLUSION: Food sensitization in the first 2 years of life can identify children at high risk of subsequent allergic disease who may benefit from early life preventive strategies. However, due to potential residual confounding in the majority of studies combined with lack of follow-up into adolescence and adulthood, further research is needed.

Residential greenness is differentially associated with childhood allergic rhinitis and aeroallergen sensitization in seven birth cohorts.

BACKGROUND: The prevalence of allergic rhinitis is high, but the role of environmental factors remains unclear. We examined cohort-specific and combined associations of residential greenness with allergic rhinitis and aeroallergen sensitization based on individual data from Swedish (BAMSE), Australian (MACS), Dutch (PIAMA), Canadian (CAPPS and SAGE), and German (GINIplus and LISAplus) birth cohorts (n = 13 016). METHODS: Allergic rhinitis (doctor diagnosis/symptoms) and aeroallergen sensitization were assessed in children aged 6-8 years in six cohorts and 10-12 years in five cohorts. Residential greenness was defined as the mean Normalized Difference Vegetation Index (NDVI) in a 500-m buffer around the home address at the time of health assessment. Cohort-specific associations per 0.2 unit increase in NDVI were assessed using logistic regression models and combined in a random-effects meta-analysis. RESULTS: Greenness in a 500-m buffer was positively associated with allergic rhinitis at 6-8 years in BAMSE (odds ratio = 1.42, 95% confidence interval [1.13, 1.79]) and GINI/LISA South (1.69 [1.19, 2.41]) but inversely associated in GINI/LISA North (0.61 [0.36, 1.01]) and PIAMA (0.67 [0.47, 0.95]). Effect estimates in CAPPS and SAGE were also conflicting but not significant (0.63 [0.32, 1.24] and 1.31 [0.81, 2.12], respectively). All meta-analyses were nonsignificant. Results were similar for aeroallergen sensitization at 6-8 years and both outcomes at 10-12 years. Stratification by NO2 concentrations, population density, an urban vs rural marker, and moving did not reveal consistent trends within subgroups. CONCLUSION: Although residential greenness appears to be associated with childhood allergic rhinitis and aeroallergen sensitization, the effect direction varies by location.