Mediterranean-Type Diets as a Protective Factor for Asthma and Atopy.

We are currently riding the second wave of the allergy epidemic, which is ongoing in affluent societies, but now also affecting developing countries. This increase in the prevalence of atopy/asthma in the Western world has coincided with a rapid improvement in living conditions and radical changes in lifestyle, suggesting that this upward trend in allergic manifestations may be associated with cultural and environmental factors. Diet is a prominent environmental exposure that has undergone major changes, with a substantial increase in the consumption of processed foods, all across the globe. On this basis, the potential effects of dietary habits on atopy and asthma have been researched rigorously, but even with a considerable body of evidence, clear associations are far from established. Many factors converge to obscure the potential relationship, including methodological, pathophysiological and cultural differences. To date, the most commonly researched, and highly promising, candidate for exerting a protective effect is the so-called Mediterranean diet (MedDi). This dietary pattern has been the subject of investigation since the mid twentieth century, and the evidence regarding its beneficial health effects is overwhelming, although data on a correlation between MedDi and the incidence and severity of asthma and atopy are inconclusive. As the prevalence of asthma appears to be lower in some Mediterranean populations, it can be speculated that the MedDi dietary pattern could indeed have a place in a preventive strategy for asthma/atopy. This is a review of the current evidence of the associations between the constituents of the MedDi and asthma/atopy, with emphasis on the pathophysiological links between MedDi and disease outcomes and the research pitfalls and methodological caveats which may hinder identification of causality. MedDi, as a dietary pattern, rather than short-term supplementation or excessive focus on single nutrient effects, may be a rational option for preventive intervention against atopy and asthma.

Occupational buckwheat allergy as a cause of allergic rhinitis, asthma, contact urticaria and anaphylaxis-An emerging problem in food-handling occupations?

Buckwheat is a known, though uncommon, allergen in occupational settings. It has recently gained popularity as healthy food and as an ingredient in gluten-free diets. We describe a series of six patient cases with occupational immediate allergy to buckwheat. Three cooks, two bakers, and a worker in a grocery store were occupationally exposed to buckwheat flour and developed immediate allergy to buckwheat, which was confirmed by skin prick testing and measurement of specific immunoglobulin E antibodies. Four of the patients were diagnosed with occupational asthma, four with occupational rhinitis, and two with occupational contact urticaria caused by buckwheat. Three of the six patients suffered anaphylaxis as consequence of their occupational buckwheat allergy after ingestion of food that contained buckwheat. The high rate of life-threatening reactions, together with a short exposure time to buckwheat before sensitization occurred in these cases, highlights the importance of a detailed occupational history and a high index of suspicion for occupational food allergens.

The Influence of Dietary Fatty Acids on Immune Responses.

Diet-derived fatty acids (FAs) are essential sources of energy and fundamental structural components of cells. They also play important roles in the modulation of immune responses in health and disease. Saturated and unsaturated FAs influence the effector and regulatory functions of innate and adaptive immune cells by changing membrane composition and fluidity and by acting through specific receptors. Impaired balance of saturated/unsaturated FAs, as well as n-6/n-3 polyunsaturated FAs has significant consequences on immune system homeostasis, contributing to the development of many allergic, autoimmune, and metabolic diseases. In this paper, we discuss up-to-date knowledge and the clinical relevance of the influence of dietary FAs on the biology, homeostasis, and functions of epithelial cells, macrophages, dendritic cells, neutrophils, innate lymphoid cells, T cells and B cells. Additionally, we review the effects of dietary FAs on the pathogenesis of many diseases, including asthma, allergic rhinitis, food allergy, atopic dermatitis, rheumatoid arthritis, multiple sclerosis as well as type 1 and 2 diabetes.

Association of pediatric obesity and asthma, pulmonary physiology, metabolic dysregulation, and atopy; and the role of weight management.

Introduction: Obesity affects about 40% of US adults and 18% of children. Its impact on the pulmonary system is best described for asthma. Areas covered: We reviewed the literature on PubMed and Google Scholar databases and summarize the effect of obesity, its associated metabolic dysregulation and altered systemic immune responses, and that of weight gain and loss on pulmonary mechanics, asthma inception, and disease burden. We include a distinct approach for diagnosing and managing the disease, including pulmonary function deficits inherent to obesity-related asthma, in light of its poor response to current asthma medications. Expert opinion: Given the projected increase in obesity, obesity-related asthma needs to be addressed now. Research on the contribution of metabolic abnormalities and systemic immune responses, intricately linked with truncal adiposity, and that of lack of atopy, to asthma disease burden, and pulmonary function deficits among obese children is fairly consistent. Since current asthma medications are more effective for atopic asthma, investigation for atopy will guide management by distinguishing asthma responsive to current medications from the non-responsive disease. Future research is needed to elucidate mechanisms by which obesity-mediated metabolic abnormalities and immune responses cause medication non-responsive asthma, which will inform repurposing of medications and drug discovery.

The role of antimicrobial treatment during pregnancy on the neonatal gut microbiome and the development of atopy, asthma, allergy and obesity in childhood.

INTRODUCTION: The use of antibiotics prenatally, during pregnancy, or neonatally may have adverse effects on the neonatal gut microbiome, and adversely affect the development of the infant immune system, leading to childhood atopy, asthma, allergy and obesity. AREAS COVERED: Vaginal eubiosis and dysbiosis from molecular-based, cultivation-independent techniques, and how this affects the neonatal gut microbiome and early development of the immune system, the association between maternal antibiotics and the beneficial role of vitamin D in the development of atopy, asthma, allergy and obesity, efforts to reduce the use of antibiotics in pregnancy and therapeutic interventions such as vaginal 'seeding', probiotics, breastfeeding and neonatal dietary supplementation. EXPERT OPINION: Currently available research gives insufficient attention to confounding variables. There remains uncertainty as to whether it is relevant that the mother suffered from the same condition as the purported infant outcome variable, for which she may have received antibiotics. In most studies, there is a lack of control for the number of antibiotic courses administered, the timing of use, the use of broad spectrum or narrow range antibiotics, the indication for antibiotics, the dose-dependent nature of the effect, the class of antibiotics used, or a varying degree of risk.

High exposure to endotoxin in farming is associated with less new-onset pollen sensitisation.

OBJECTIVES: Little is known about risk factors for new onset and loss of atopic sensitisation in adulthood. The aim is to examine the longitudinal effect of quantitatively assessed endotoxin exposures on changes in specific allergen sensitisation in young adults. METHODS: The cohort consisted of 1113 young Danish farmers and rural controls, with a mean age of 19 years at baseline. Sensitisation to birch pollen, grass pollen, cat dander and house dust mite was measured by specific IgE levels in serum samples from baseline and at 15 years' follow-up. Changes in sensitisation were analysed in relation to cumulative endotoxin exposure during follow-up, considering early life farm exposure. RESULTS: Endotoxin exposure during follow-up was significantly associated with less new onset of specifically grass and birch pollen sensitisation. For the highest versus lowest quartile of cumulative endotoxin exposure, the OR for new-onset IgE sensitisation was 0.35 (0.13-0.91) for birch and 0.14 (0.05-0.50) for grass. On the other hand, loss of pollen sensitisation showed a positive, although mostly non-significant, association with increased levels of endotoxin exposure. Endotoxin exposure was not associated with significant changes in cat dander and house dust mite sensitisation. CONCLUSIONS: High exposure to endotoxin during young adulthood appears to protect against new onset of pollen sensitisation, independent of childhood farm exposure.

An approach to allergy risk assessments for e-liquid ingredients.

Many flavours and fragrances are known allergens. Their selection and inclusion levels in e-liquids must therefore be guided by toxicological principles, taking into account the exposure pattern and inhalation route of exposure. For contact sensitisation, a general, agreed quantitative risk assessment approach to prevent dermal sensitisation exists. Here we propose exposure parameters and safety factors to apply this approach to e-liquid ingredients. Additionally, as a risk management approach for pre-sensitised individuals, we derive a threshold of 0.1% for indicating the presence of a contact sensitiser in e-liquid. Risk assessment for respiratory sensitisation is not well established. Occupational exposure limits that protect against respiratory allergy are generally very low. Cocoa shell extract is used as a case study to discuss the issues. A tolerable exposure level is derived and estimates of consumer exposure are presented, leading to the practical risk management approach of excluding respiratory sensitisers as e-liquid ingredients. Related to this, if natural extracts are used as flavourings in e-liquids, we recommend only protein-free versions are used. Additionally, we recommend the presence of any potential food allergens should be noted on the product information.

Vitamin D supplementation during pregnancy and infancy reduces aeroallergen sensitization: a randomized controlled trial.

BACKGROUND: Vitamin D has immune-modulating effects. We determined whether vitamin D supplementation during pregnancy and infancy prevents aeroallergen sensitization and primary care respiratory illness presentations. METHODS: A randomized, double-blind, placebo-controlled parallel-group trial. We assigned pregnant women, from 27-week gestation to birth, and then their infants, from birth to 6 months, to placebo or one of two dosages of daily oral vitamin D. Woman/infant pairs were randomized to: placebo/placebo, 1000 IU/400 IU or 2000 IU/800 IU. When the children were 18 months old, we measured serum-specific IgE antibodies and identified acute primary care visits described by the doctor to be due to a cold, otitis media, an upper respiratory infection, croup, asthma, bronchitis, bronchiolitis, a wheezy lower respiratory infection or fever and cough. RESULTS: Specific IgE was measured on 185 of 260 (71%) enrolled children. The proportion of children sensitized differed by study group for four mite antigens: Dermatophagoides farinae (Der-f1, Der-f2) and Dermatophagoides pteronyssinus (Der-p1, Der-p2). With results presented for placebo, lower dose, and higher dose vitamin D, respectively (all P < 0.05): Der-f1 (18%, 10%, 2%), Der-f2 (14%, 3%, 2%), Der-p1 (19%, 14%, 3%) and Der-p2 (12%, 2%, 3%). There were study group differences in the proportion of children with primary care visits described by the doctor as being for asthma (11%, 0%, 4%, P = 0.002), but not for the other respiratory diagnoses. CONCLUSIONS: Vitamin D supplementation during pregnancy and infancy reduces the proportion of children sensitized to mites at age 18 months. Preliminary data indicate a possible effect on primary care visits where asthma is diagnosed.

Comparison of microneedles and adhesive-tape stripping in skin preparation for epicutaneous allergen delivery.

BACKGROUND: Epicutaneous immunotherapy targets the network of dendritic cells in the epidermis. Allergen exposure of the dermal layers should be limited as these contain mast cells and blood vessels, which increases the risk for local and systemic allergic reactions. METHODS: This intraindividually controlled trial included 20 subjects with birch pollen allergy. Three areas of the volar forearms were treated by repeated adhesive-tape stripping, single-prick lancet piercing and microneedle array application. Four 10-fold dilutions of allergen extract were applied to each area and the IgE-mediated immediate-phase reactions and cell-mediated eczema were assessed. RESULTS: Allergen application after tape stripping led to an immediate-phase reaction in 2 subjects (10%) at the highest allergen concentration of 10 HEP/ml. Both prick needle and microneedle pretreatment resulted in immediate-phase reactions in all subjects (100%). The reactivity pattern, however, differed significantly: 95% of the reactions after pricking occurred at concentrations of ≤0.1 HEP/ml, whereas 50% of the reactions after microneedle preparation were noted at ≥1 HEP/ml. In 3 subjects (15%), eczema was observed on the microneedle-treated skin area. No serious adverse events occurred. CONCLUSIONS: Microneedles enhance stratum corneum penetration when compared to tape stripping. However, they do not resolve the problem of mast cell-mediated local reactions, possibly due to diffusion into the dermis. The occurrence of eczema after the microneedle treatment suggests induction of dendritic cell-mediated T cell responses. Therefore, skin preparation with microneedles may be a promising method for epicutaneous allergen immunotherapy.

Neonatal vitamin A supplementation associated with increased atopy in girls.

BACKGROUND: Neonatal vitamin A supplementation (NVAS) is currently being considered as policy in countries at risk of deficiency. A previous study suggested that NVAS may be associated with increased atopy. We examined the effect of NVAS on atopy by conducting long-term follow-up of a previous randomized controlled trial in Guinea-Bissau. METHODS: In 2002-2004, we randomized 4345 normal birthweight neonates to NVAS (50 000 IU retinyl palmitate) or placebo together with their Bacillus Calmette-Guérin vaccination. In 2013, we visited the 1692 (39%) children now aged 8-10 years who were still living in the study area, and 1478 (87%) were found at home. Provided consent, a skin prick test was performed, and history of allergic symptoms was recorded. Associations of NVAS and atopy (defined as skin prick test reaction of ≥3 mm) were analysed using binomial regression. RESULTS: Of the 1430 children with a valid skin prick test, 228 (16%) were positive (more boys (20%) than girls (12%), P-value < 0.0001). NVAS did not increase the overall risk of atopy (RR 1.10 [95% CI 0.87-1.40]). However, NVAS was associated with significantly increased risk among females (RR 1.78 [1.17-2.72]) but not among males (0.86 [0.64-1.15], P-value for interaction between NVAS and gender = 0.005). Furthermore, NVAS was associated with increased risk of wheezing among females (RR 1.80 [1.03-3.17], but not among males, P-value for interaction = 0.05). CONCLUSION: The study corroborated previous observations; NVAS was associated with increased risk of atopy and wheezing, in this study only among females. Further studies on NVAS and atopy are warranted.

Omega-3 fatty acids and asthma in children.

The purpose of this study was to summarize and analyze the results of studies supporting the use of omega-3 fatty acids for their therapeutic and preventive value in childhood asthma in light of recent genetic evidence strongly suggesting a pathogenetic role in asthma and to discuss the implications of these findings for future research. Although a considerable number of observational studies have been conducted in children showing a beneficial effect of omega-3 dietary intake in asthma, a fully well-designed, rigorously conducted investigational study is still lacking. Additionally, the few interventional trials with omega-3 supplementation conducted in asthmatic children have often yielded conflicting results. The genetic polymorphism and the gene-nutritional interactions that accompany asthma can be the missing factors and may explain the inconsistent results found in these interventional trials. Therefore, the analyses of key genes variants should be included in future studies to thoroughly investigate the effects of long-chain polyunsaturated fatty acid on asthma. Although a definitive conclusion can not be made supporting a beneficial effect of dietary modification or supplementation with omega-3 for the prevention or modification of asthmatic disease in children, there is sufficient evidence to support this possibility. There is, therefore, a clear need for future research to investigate the feasibility of this dietetic approach to reduce the likely development of asthma and/or the successful treatment of asthmatic disease. From a public health perspective, if a dietetic approach is successfully documented, even if only in a cohort of susceptible individuals, it would offer a far better management tool than currently available, better tolerated, and, in the long run, more cost-effective.

Vitamin A supplementation and risk of atopy: long-term follow-up of a randomized trial of vitamin A supplementation at six and nine months of age.

BACKGROUND: The World Health Organization recommends high-dose vitamin A supplementation (VAS) for children above six months of age in low-income countries. VAS has been associated with up-regulation of the Th2 response. We aimed to determine if VAS is associated with atopy in childhood. METHODS: Infants in Guinea-Bissau were randomly allocated VAS or placebo, either at six and nine months of age, or only at nine months of age. At six months of age, children were furthermore randomized to measles vaccine or inactivated polio vaccine. At nine months of age all children received measles vaccine. Children were revisited seven years later and skin prick testing was performed. Atopy was defined as a skin prick reaction ≥ 3 mm. RESULTS: 40 of 263 children (15%) were atopic. Overall VAS had no significant effect on the risk of atopy (Prevalence Ratio 1.23; 95% CI 0.69-2.18). The Prevalence Ratio was 1.60 (0.66-3.90) for males and 1.00 (0.46-2.15) for females. CONCLUSIONS: There was no significant effect of VAS in infancy on atopy later in childhood. The role of infant VAS in the development of atopy is still unclear.

Vitamin A supplementation and BCG vaccination at birth may affect atopy in childhood: long-term follow-up of a randomized controlled trial.

BACKGROUND: Recent evidence suggests that immunogenic interventions such as vaccines and micronutrients may affect atopic sensitization and atopic disease. We aimed to determine whether neonatal BCG vaccination, vitamin A supplementation and other vaccinations affect atopy in childhood. METHODS: In Guinea-Bissau, low-birthweight infants were randomized to early (intervention) or delayed (usual policy) BCG. A subgroup was also randomly assigned vitamin A supplementation or placebo in a two-by-two factorial design. Participants were followed up at age 3-9 years. The main outcome was atopy defined as skin prick test reaction ≥3 mm. Secondary outcomes were symptoms of eczema, asthma and food allergy. RESULTS: Two hundred eighty-one children had valid skin prick tests performed, and 14% (39/281) were atopic. There was no significant difference in atopy between the early and delayed BCG groups (OR, 0.71; 95% CI, 0.34-1.47). Atopy was significantly reduced in children who had responded to BCG with a scar (OR, 0.42; 0.19-0.94). Vitamin A supplementation was associated with increased atopy (OR, 2.88; 1.26-6.58), especially in those who received simultaneous BCG (5.99; 1.99-18.1, P = 0.09 for interaction between vitamin A supplementation and BCG). Early vs delayed BCG was not associated with symptoms of atopic disease, but vitamin A supplementation increased odds of wheeze within the past 12 months (OR, 2.45; 1.20-4.96). CONCLUSIONS: There were no statistically significant effects of early vs delayed BCG on atopy or symptoms of atopic disease. Having a BCG scar was associated with reduced atopy, whereas neonatal vitamin A supplementation was associated with increased atopy. STUDY REGISTRATION: Clinicaltrials.gov NCT 01420705.

Immunotherapy safety: what have we learned from surveillance surveys?

Subcutaneous allergen immunotherapy (SCIT) is beneficial for the treatment of allergic rhinitis, asthma, and in preventing stinging insect anaphylaxis, but is not without risks. Four retrospective surveillance surveys and one on-going national prospective study have attempted to characterize the incidence and risk factors for fatal and non-fatal SCIT reactions. These studies have contributed significantly to currently recommended SCIT safety guidelines. Recent surveillance studies indicate stable SR rates, and a possible decline in the incidence of fatal reactions since the implementation of evidence-based safety guidelines. This review will provide a detailed summary of the evidence from surveillance studies for risk factors associated with SCIT reactions, including: uncontrolled asthma, prior systemic reactions, dosing during peak pollen seasons, epinephrine being delayed or not given, dosing or administration errors, inadequate waiting times, reactions occurring more than 30 min after injections, injections given in medically unsupervised settings, concomitant beta-blocker and angiotensin-converting enzyme inhibitor (ACEi) use, and accelerated build-up regimens.

Cedar and cypress pollen counts are associated with the prevalence of allergic diseases in Japanese schoolchildren.

BACKGROUND: Patients allergic to pollen have been known to become more symptomatic during pollen season compared with the nonpollen season. However, there are few studies regarding whether higher exposure to pollen might increase the prevalence of allergic diseases. METHODS: An ecological analysis was conducted to evaluate whether pollen exposure is associated with the prevalence of allergic diseases in schoolchildren. Pollen count data of Japanese cedar (Cryptomeria japonica) and Japanese cypress (Chamaecyparis obtusa), which are the major pollen allergens in Japan, were obtained from each prefecture. The prevalence of allergic diseases in schoolchildren in each prefecture was based on a nationwide cross-sectional survey using the International Study of Asthma and Allergies in Childhood questionnaire. RESULTS: After omitting three prefectures where pollen data were not available, data of 44 prefectures were analysed. The prevalence of allergic rhinoconjunctivitis in children aged 6-7 years was positively associated with both cedar and cypress pollen counts (P = 0.01, both), whereas the prevalence of allergic rhinoconjunctivitis in children aged 13-14 years was positively associated with only cypress pollen counts (P = 0.003). Furthermore, the prevalence of asthma was positively associated with cedar pollen counts in 6- to 7-year-old children (P = 0.003) but not cypress pollen counts in either age group. CONCLUSIONS: There are ecological associations between pollen counts and the prevalence of allergic diseases in Japanese schoolchildren. Further studies are needed to determine whether the difference between the effects of cedar and cypress pollens is attributable to pollen counts or allergenicity.

Evidence for primary laryngeal inhalant allergy: a randomized, double-blinded crossover study.

BACKGROUND: Despite anecdotal reports, no controlled studies to date link allergen exposure with a change in vocal function or dysphonia. The aim of this study was to determine whether allergen exposure in susceptible individuals impairs vocal function. METHODS: The study was a prospective, double-blind, placebo-controlled study in which subjects serve as their own controls. The participants were 5 inhalant allergic adults with suspected dysphonia from allergies, without evidence of reactive lower airways based on methacholine challenge. All subjects were exposed to 2 experimental conditions in which they were challenged with (1) orally inhaled diluent placebo on 1 day, and (2) orally inhaled allergen on another day. Conditions were randomly ordered across subjects and separated by at least 48 hours. Phonatory threshold pressure (PTP) at the 80th percentile pitch was measured prior to diluent and allergen challenge, and 15 and 60 minutes postchallenge to assess potential change in vocal function after challenge testing. RESULTS: A repeated measures ANOVA revealed a significant main effect for treatment (allergen vs placebo, p = 0.013) with greater PTP required post-allergen challenge compared to placebo and an effect size of 0.821. CONCLUSION: A primary causal relationship between allergen exposure and impaired vocal function, as assessed by PTP, was observed in adults with documented allergy independent of asthma or nasal exposure. The current design establishes a safe model for laryngeal inhalant allergen challenge.