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.

A Review of the Respiratory Health Burden Attributable to Short-Term Exposure to Pollen.

Respiratory diseases such as asthma, allergic rhinitis (AR) and chronic obstructive pulmonary disease (COPD) affect millions worldwide and pose a significant global public health burden. Over the years, changes in land use and climate have increased pollen quantity, allergenicity and duration of the pollen season, thus increasing its impact on respiratory disease. Many studies have investigated the associations between short-term ambient pollen (i.e., within days or weeks of exposure) and respiratory outcomes. Here, we reviewed the current evidence on the association between short-term outdoor pollen exposure and thunderstorm asthma (TA), asthma and COPD hospital presentations, general practice (GP) consultations, self-reported respiratory symptoms, lung function changes and their potential effect modifiers. The literature suggests strong evidence of an association between ambient pollen concentrations and almost all respiratory outcomes mentioned above, especially in people with pre-existing respiratory diseases. However, the evidence on sub-clinical lung function changes, COPD, and effect modifiers other than asthma, hay fever and pollen sensitisation are still scarce and requires further exploration. Better understanding of the implications of pollen on respiratory health can aid healthcare professionals to implement appropriate management strategies.

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.

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.

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.