Is antenatal or early-life vitamin D associated with eczema or food allergy in childhood? A systematic review.

OBJECTIVE: To summarise the associations between antenatal or early-life blood vitamin D and the development of eczema/food allergy in childhood. DESIGN: A systematic review and meta-analyses were conducted to synthesize the published literature. Two reviewers independently performed the study selection and data extraction on Covidence. We assessed the risk of bias for observational studies by using the Newcastle-Ottawa Scale and the Cochrane Risk of Bias tool for clinical trials. The certainty of the evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). DATA SOURCES: We systematically searched PubMed and Embase from inception and April 2022. ELIGIBILITY CRITERIA: Human studies that investigated prospective associations between antenatal or early-life blood vitamin D levels, dietary intake or supplementation and childhood eczema/food allergy. RESULTS: Forty-three articles including six randomised controlled trials (RCTs) were included. Four RCTs of vitamin D supplementation during pregnancy showed no evidence of an effect on the incidence of eczema (pooled odds ratio [OR] = 0.85; 0.67-1.08, I2  = 6.7%, n = 2074). Three RCTs reported null associations between supplementation in pregnancy/infancy and food allergy. From six cohort studies, increasing cord blood vitamin D levels were associated with reduced prevalence of eczema at/close to age one (OR per 10 nmol/L increase = 0.89; 0.84-0.94, I2  = 0%, 2025 participants). We found no evidence of an association between maternal antenatal or infant vitamin D level or dietary intake and the development of food allergy or eczema in offspring. CONCLUSIONS: We found an association between higher vitamin D levels in cord blood and reduced risk of eczema in cohort studies. Further trials with maternal and infant supplementation are needed to confirm if vitamin D supplementation can effectively prevent eczema or food allergy in childhood. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, No. CRD42013005559.

The role of short-term grass pollen exposure in food skin-prick test reactivity, food allergy, and eczema flares in children.

BACKGROUND: While the relationship between pollen and respiratory allergies is well-documented, the role of short-term pollen exposure in food allergy and eczema flares has not previously been explored. We aimed to investigate these associations in a population-based sample of children. METHODS: We investigated 1- (n = 1108) and 6-year-old (n = 675) children in the grass pollen season from the HealthNuts cohort. Grass pollen concentrations were considered on the day of testing (lag 0), up to three days before (lag 1-lag 3) and cumulatively (lag 0-3). Associations between grass pollen and food skin-prick test reactivity (SPT ≥ 2 mm at age 1 year and ≥ 3 mm at age 6 years), eczema flares, challenge-confirmed food allergy, reaction threshold to oral food challenges (OFC), and serum food-specific IgE levels were analyzed using either logistic or quantile regression models. Atopy and family history of allergic disease were considered as potent effect modifiers. RESULTS: Grass pollen at lag 0-3 (every 20 grains/m3 increase) was associated with an up to 1.2-fold increased odds of food SPT reactivity and eczema flares in 6-year-olds. In 1-year-olds, the associations were only observed for peanut in those with a family history of food allergy. Increasing grass pollen concentrations were associated with a lower reaction threshold to OFC and higher serum IgE levels in peanut-allergic 1-year-olds only. CONCLUSION: Increasing grass pollen concentration was associated with increased risk of food SPT reactivity and eczema flares in children. The associations in peanut-allergic infants may be related to immune activation and/or peanut and grass pollen cross-reactivity leading to a lower reaction threshold.

Children With Food Allergy Are at Risk of Lower Lung Function on High-Pollen Days.

BACKGROUND: Grass pollen exposure is a risk factor for childhood asthma hospital attendances. However, its short-term influence on lung function, especially among those with other allergic conditions, has been less well-studied. OBJECTIVE: To investigate this association in a population-based sample of children. METHODS: Within the HealthNuts cohort, 641 children performed spirometry during the grass pollen season. Grass pollen concentration was considered on the day of testing (lag 0), up to 3 days before (lag 1-lag 3), and cumulatively (lag 0-3). We used linear regression to assess the relevant associations and examined potential interactions with current asthma, hay fever or eczema, and food allergy. RESULTS: Associations were observed only in children with allergic disease (P value for interaction ≤ 0.1). In children with food allergy, grass pollen concentration was associated with a lower ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) and lower mid-forced expiratory flows (FEF25%-75%) at all lags (eg, at lag 2, FEV1/FVC z-score = -0.50 [95% CI -0.80 to -0.20] and FEF25%--75% z-score = -0.40 [-0.60 to -0.04] per 20 grains/m3 pollen increase), and increased bronchodilator responsiveness (BDR) at lag 2 and lag 3 (eg, at lag 2, BDR = (31 [95% CI -0.005 to 62] mL). In children with current asthma, increasing grass pollen concentration was associated with lower FEF25%-75% and increased BDR, whereas children with current hay fever or eczema had increased BDR only. CONCLUSIONS: A proactive approach needs to be enforced to manage susceptible children, especially those with food allergy, before high-grass pollen days.

Associations between grass pollen exposures in utero and in early life with food allergy in 12-month-old infants.

Birth during pollen seasons may influence food allergy risk but no study has assessed pollen exposure. Using the HealthNuts population-based cohort of 5276 infants, we assessed grass pollen exposures, in utero and up to the first 6 months of life, on hen's egg, sesame and peanut allergy outcomes at 12 months. Cumulative pollen exposure in the first 7 days of life increased risk of peanut sensitization aMOR (adjusted multinomial odds ratio) = 1.21 (95% CI: 1.01-1.44). Exposure between first 4-6 months of life increased risk of hen's egg aMOR = 1.02 (95% CI: 1.004-1.04) and sensitization to all foods aMOR = 1.02 (95% CI: 1.003-1.04). Grass pollen exposure was associated with food challenge diagnosed food allergy, but only among infants with a maternal history of food allergy. Exposure to grass pollen in the intrauterine period and infancy may be important but more studies are needed to replicate these findings.

Childhood lung function as a determinant of menopause-dependent lung function decline.

RATIONALE: The naturally occurring age-dependent decline in lung function accelerates after menopause, likely due to the change of the endocrine balance. Although increasing evidence shows suboptimal lung health in early life can increase adult  susceptibility to insults, the potential effect of poor childhood lung function on menopause-dependent lung function decline has not yet been investigated. OBJECTIVES: To study whether menopause-dependent lung function decline, assessed as forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), is determined by childhood lung function. METHODS: The Tasmanian Longitudinal Health Study, a cohort born in 1961, underwent spirometry at age seven.  At ages 45 and 50 serum samples, spirometry and questionnaire data were collected (N = 506). We measured follicle stimulating and luteinizing hormones to determine menopausal status using latent profile analysis. The menopause-dependent lung function decline was investigated using linear mixed models, adjusted for anthropometrics, occupational level, smoking, asthma, asthma medication and study year, for the whole study population and stratified by tertiles of childhood lung function. MEASUREMENTS AND MAIN RESULTS: The overall menopause-dependent lung function decline was 19.3 mL/y (95%CI 2.2 to 36.3) for FVC and 9.1 mL/y (-2.8 to 21.0) for FEV1. This was most pronounced (pinteraction=0.03) among women within the lowest tertile of childhood lung function [FVC 22.2 mL/y (1.1 to 43.4); FEV1 13.9 mL/y (-1.5 to 29.4)]. CONCLUSIONS: Lung function declines especially rapidly in postmenopausal women who had poor low lung function in childhood. This provides novel insights into respiratory health during reproductive aging and emphasizes the need for holistic public health strategies covering the whole lifespan.

Human milk oligosaccharide profiles and allergic disease up to 18 years.

BACKGROUND: Human milk oligosaccharides (HMO) are a diverse range of sugars secreted in breast milk that have direct and indirect effects on immunity. The profiles of HMOs produced differ between mothers. OBJECTIVE: We sought to determine the relationship between maternal HMO profiles and offspring allergic diseases up to age 18 years. METHODS: Colostrum and early lactation milk samples were collected from 285 mothers enrolled in a high-allergy-risk birth cohort, the Melbourne Atopy Cohort Study. Nineteen HMOs were measured. Profiles/patterns of maternal HMOs were determined using LCA. Details of allergic disease outcomes including sensitization, wheeze, asthma, and eczema were collected at multiple follow-ups up to age 18 years. Adjusted logistic regression analyses and generalized estimating equations were used to determine the relationship between HMO profiles and allergy. RESULTS: The levels of several HMOs were highly correlated with each other. LCA determined 7 distinct maternal milk profiles with memberships of 10% and 20%. Compared with offspring exposed to the neutral Lewis HMO profile, exposure to acidic Lewis HMOs was associated with a higher risk of allergic disease and asthma over childhood (odds ratio asthma at 18 years, 5.82; 95% CI, 1.59-21.23), whereas exposure to the acidic-predominant profile was associated with a reduced risk of food sensitization (OR at 12 years, 0.08; 95% CI, 0.01-0.67). CONCLUSIONS: In this high-allergy-risk birth cohort, some profiles of HMOs were associated with increased and some with decreased allergic disease risks over childhood. Further studies are needed to confirm these findings and realize the potential for intervention.

Is short-term exposure to grass pollen adversely associated with lung function and airway inflammation in the community?

BACKGROUND: The association between grass pollen exposure and early markers of asthma exacerbations such as lung function changes and increase in airway inflammation is limited. We investigated the associations between short-term grass pollen exposure and lung function and airway inflammation in a community-based sample, and whether any such associations were modified by current asthma, current hay fever, pollen sensitization, age, and other environmental factors. METHODS: Cross-sectional and short-term analyses of data from the Melbourne Atopy Cohort Study (MACS) participants (n = 936). Lung function was assessed using spirometry. Airway inflammation was assessed by fractional exhaled nitric oxide (FeNO) and exhaled breath condensate pH and nitrogen oxides (NOx). Daily pollen counts were collected using a volumetric spore trap. The associations were examined by linear regression. RESULTS: Higher ambient levels of grass pollen 2 days before (lag 2) were associated with lower mid-forced expiratory flow (FEF25%-75% ) and FEV1 /FVC ratio (Coef. [95% CI] = -119 [-226, -11] mL/s and -1.0 [-3.0, -0.03] %, respectively) and also 3 days before (lag 3). Increased levels of grass pollen a day before (lag 1) were associated with increased FeNO (4.35 [-0.1, 8.7] ppb) and also at lag 2. Adverse associations between pollen and multiple outcomes were greater in adults with current asthma, hay fever, and pollen sensitization. CONCLUSION: Grass pollen exposure was associated with eosinophilic airway inflammation 1-2 days after exposure and airway obstruction 2-3 days after exposure. Adults and individuals with asthma, hay fever, and pollen sensitization may be at higher risk.

A systematic review of the role of grass pollen and fungi in thunderstorm asthma.

BACKGROUND: Thunderstorm asthma is defined as epidemics of asthma occurring shortly after a thunderstorm. While grass pollen has been implicated in thunderstorm asthma events, little is known about the role of fungi and studies have not been synthesised. OBJECTIVE: This systematic review aims to evaluate whether grass pollen is necessary in thunderstorm asthma events and whether fungi also play a part in these associations. METHODS: We conducted a systematic search using six electronic databases (i.e. CINAHL, Medline (Ovid), Web of Science, ProQuest Central, EMBASE and Google Scholar) and checked reference lists. The search terms used were pollen AND thunderstorm* AND asthma. The inclusion criteria were studies published in English with original human data relating to outdoor pollen and thunderstorm asthma. RESULTS: Twenty of 2198 studies were eligible. Reported findings differed due to variation in methodological approaches and a meta-analysis was not possible. Nonetheless, of the 20 studies included, 15 demonstrated some relationship with nine demonstrating lagged effects up to four days for increasing grass pollen counts associated with increased risk of thunderstorm asthma. Of the 10 studies that examined fungi, nine demonstrated a positive relationship with thunderstorm asthma. The fungal taxa involved varied, depending on whether measurements were recorded before, during or after the thunderstorm. Nevertheless, none of the studies considered fungi as a potential effect modifier for the pollen-thunderstorm asthma association. CONCLUSION: We found evidence to suggest that grass pollen was a necessary factor for thunderstorm asthma but there are other as yet unrecognised environmental factors that may also be important. Further research is required to examine the role of fungi and other environmental factors such as air quality as potential effect modifiers of the association.

Pollen exposure at birth and adolescent lung function, and modification by residential greenness.

BACKGROUND: Exposure to high levels of pollen in infancy is a risk factor for allergic respiratory diseases in later childhood, but effects on lung function are not fully understood. We aim to examine associations between grass pollen exposure in the first months of life and lung function at 12 and 18 years, and explore potential modification. METHODS: Using the Melbourne Atopy Cohort Study, a birth cohort of children with a family history of allergic diseases, we modeled the association between cumulative grass pollen exposure up to 3 months after birth, on FEV1 , FVC, and FEV1 /FVC ratio at 12 and 18 years. We also assessed modifying effects of residential greenness levels (derived from satellite imagery), asthma, and early life sensitization to ryegrass. RESULTS: Grass pollen exposure in the first 7 days was associated with a reduction in FEV1 (-15.5 mL; 95% CI: -27.6, -3.3 per doubling of pollen count) and FVC (-20.8 mL; -35.4, -6.1) at 12 years, but not at 18 years. Increase in cumulative grass pollen exposure up to 3 months was negatively associated with FVC at 12 and 18. Exposure to high residential greenness modified the association at 18 years. CONCLUSION: Early exposure to grass pollen was associated with decreased lung function in children and adolescents. Targeted interventions for pollen avoidance strategies that take into account local topography could be implemented alongside other clinical interventions such as immunotherapy.

Environmental grass pollen levels in utero and at birth and cord blood IgE: Analysis of three birth cohorts.

BACKGROUND: Early life factors are associated with allergic respiratory diseases, but the role of high grass pollen concentrations during pregnancy and shortly after birth is not known. OBJECTIVE: To assess outdoor levels of grass pollen during the intrauterine period and at birth during peak pollen season on cord blood IgE in birth cohorts. METHODS: Three birth cohorts were included: MACS (n = 429), Australia; COPSAC2000 (n = 200), Denmark; and LISA (n = 1968), Germany. Cord blood IgE was categorized (<0.5 kU/L, 0.5-1 kU/L, >1 kU/L) and dichotomized (high IgE ≥ 0.5 kU/L). Birth during the grass pollen season months and cumulative exposure to outdoor grass pollen counts during pregnancy with cord blood IgE were analysed using multinomial regression and analysed in meta-analysis using binomial regression adjusted for potential confounders. RESULTS: Birth during the grass pollen season had higher pooled odds of cord blood IgE >0.5 kU/L 1.37 (95% CI 1.06, 1.77) in a meta-analysis with little heterogeneity between the three cohorts. Cumulative exposure to outdoor grass pollen counts during the entire pregnancy was associated with slightly lower pooled odds but significant (OR = 0.98, 95% CI: 0.96 to 0.99). CONCLUSIONS: Birth during grass pollen seasons were associated with increased risk of high cord blood IgE in cities from both hemispheres, but high pollen loads in the environment during the entire pregnancy appeared protective. As IgE responses develop during the first months of life, our study findings provide new insights into the mechanisms of grass pollen exposure at birth and shortly after on possible allergic respiratory diseases.

The role of outdoor fungi on asthma hospital admissions in children and adolescents: A 5-year time stratified case-crossover analysis.

BACKGROUND: Some fungal spores can trigger asthma exacerbation but knowledge of which outdoor fungal spores contribute to asthma hospitalisation is limited. OBJECTIVES: To examine the role of outdoor fungal spores in child and adolescent asthma hospitalisations. METHODS: We conducted a bi-directional time-stratified case-crossover study of child and adolescent asthma hospitalisations over 5 years. Conditional logistic regression assessed the role of 20 fungi taxa (Same day [L0] and lagged [L1-3]) adjusted for maximum temperature, humidity and grass pollen. Strata specific effects were explored if there was evidence of effect modification by age, sex, air pollutants or grass pollen. Non-linear effects examined with Generalized Additive Models. RESULTS: Of 2098 children hospitalised for asthma, 60% were boys; mean age was 5.5±3.7 years. Fungal spore counts peaked during warm months. Regression models found weak associations with Coprinus [L0,L1: OR=1.03, 1.01-1.06], Periconia [L0: OR=1.03, 1.001-1.07] and Chaetomium [L2: OR=1.08, 1.0-1.2]. Sex appeared to act as an effect modifier with girls having stronger associations with Cladosporium, Coprinus and total fungi. Older adolescent (14-18 years) hospitalisation was significantly associated with Coprinus and Ustilago/smuts. Air pollutants and grass pollen did not appear to act as effect modifiers. Non-linearity was not detected. CONCLUSION: There may be associations between some outdoor fungal spores and asthma hospitalisations. Further research needed to explore whether these findings can be replicated; and examine whether fungal sensitisation and/or human rhinovirus infections are associated with stronger effects. If findings are replicated, then the need to develop predictive models for fungal spore distribution and levels may become more important.

Environmental and genetic determinants of vitamin D insufficiency in 12-month-old infants.

We aimed to investigate the relationship between genetic and environmental exposure and vitamin D status at age one, stratified by ethnicity. This study included 563 12-month-old infants in the HealthNuts population-based study. DNA from participants' blood samples was genotyped using Sequenom MassARRAY MALDI-TOF system on 28 single nucleotide polymorphisms (SNPs) in six genes. Using logistic regression, we examined associations between environmental exposure and SNPs in vitamin D pathway and filaggrin genes and vitamin D insufficiency (VDI). VDI, defined as serum 25-hydroxyvitamin D3(25(OH)D3) level ≤50nmol/L, was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Infants were stratified by ethnicity determined by parent's country of birth. Infants formula fed at 12 months were associated with reduced odds of VDI compared to infants with no current formula use at 12 months. This association differed by ethnicity (Pinteraction=0.01). The odds ratio (OR) of VDI was 0.29 for Caucasian infants (95% CI, 0.18-0.47) and 0.04 for Asian infants (95% CI, 0.006-0.23). Maternal vitamin D supplementation during pregnancy and/or breastfeeding were associated with increased odds of infants being VDI (OR, 2.39; 95% CI, 1.11-5.18 and OR, 2.5; 95% CI, 1.20-5.24 respectively). Presence of a minor allele for any GC SNP (rs17467825, rs1155563, rs2282679, rs3755967, rs4588, rs7041) was associated with increased odds of VDI. Caucasian infants homozygous (AA) for rs4588 had an OR of 2.49 of being associated with VDI (95% CI, 1.19-5.18). In a country without routine infant vitamin D supplementation or food chain fortification, formula use is strongly associated with a reduced risk of VDI regardless of ethnicity. There was borderline significance for an association between filaggrin mutations and VDI. However, polymorphisms in vitamin D pathway related genes were associated with increased likelihood of being VDI in infancy.

Overview of evidence in prevention and aetiology of food allergy: a review of systematic reviews.

The worldwide prevalence of food allergy appears to be increasing. Early life environmental factors are implicated in the aetiology of this global epidemic. The largest burden of disease is in early childhood, where research efforts aimed at prevention have been focused. Evidence synthesis from good quality systematic reviews is needed. We performed an overview of systematic reviews concerning the prevention and aetiology of food allergy, retrieving 14 systematic reviews, which covered three broad topics: formula (hydrolysed or soy) for the prevention of food allergy or food sensitization; maternal and infant diet and dietary supplements for the prevention of food allergy or food sensitization and hygiene hypothesis-related interventions. Using the AMSTAR criteria for assessment of methodological quality, we found five reviews to be of high quality, seven of medium quality and two of low quality. Overall we found no compelling evidence that any of the interventions that had been systematically reviewed were related to the risk of food allergy. Updating of existing reviews, and production of new systematic reviews, are needed in areas where evidence is emerging for interventions and environmental associations. Furthermore, additional primary studies, with greater numbers of participants and objective food allergy definitions are urgently required.

A transitional care service for elderly chronic disease patients at risk of readmission.

BACKGROUND: Multiple hospital admissions, especially those related to chronic disease, represent a particular challenge to the acute health care sector in Australia. OBJECTIVE: To determine whether a nurse-led chronic disease management model of transitional care reduced readmissions to acute care. DESIGN: A quasi-experimental controlled trial. SETTING: A large tertiary metropolitan teaching hospital. PARTICIPANTS: 166 general medical patients aged > or = 65 years with either a history of readmissions to acute care or multiple medical comorbidities. INTERVENTION: Implementation of a chronic disease management model of transitional care aimed at improving patient management and reducing readmissions to acute care. MAIN OUTCOME MEASURES: Readmission rates and emergency department presentation rates at 3-and 6-month follow up. Secondary outcome measures include quality of life, discharge destination, and primary health care service utilisation. RESULTS: There was no difference in readmission rates, emergency department presentation rates, quality of life, discharge destination or primary health care service utilisation. The difficulties inherent in evaluating this type of multifactorial intervention are discussed and consideration is given to patient factors, the difficulty of influencing readmission rates, and local system issues. CONCLUSION: The outcomes of this study reflect the tension that exists between implementing multifaceted integrated health service programs and attempting to evaluate them within complex and changing environments using robust research methodologies.