Specific gut microbiome signatures and the associated pro-inflamatory functions are linked to pediatric allergy and acquisition of immune tolerance.

Understanding the functional potential of the gut microbiome is of primary importance for the design of innovative strategies for allergy treatment and prevention. Here we report the gut microbiome features of 90 children affected by food (FA) or respiratory (RA) allergies and 30 age-matched, healthy controls (CT). We identify specific microbial signatures in the gut microbiome of allergic children, such as higher abundance of Ruminococcus gnavus and Faecalibacterium prausnitzii, and a depletion of Bifidobacterium longum, Bacteroides dorei, B. vulgatus and fiber-degrading taxa. The metagenome of allergic children shows a pro-inflammatory potential, with an enrichment of genes involved in the production of bacterial lipo-polysaccharides and urease. We demonstrate that specific gut microbiome signatures at baseline can be predictable of immune tolerance acquisition. Finally, a strain-level selection occurring in the gut microbiome of allergic subjects is identified. R. gnavus strains enriched in FA and RA showed lower ability to degrade fiber, and genes involved in the production of a pro-inflammatory polysaccharide. We demonstrate that a gut microbiome dysbiosis occurs in allergic children, with R. gnavus emerging as a main player in pediatric allergy. These findings may open new strategies in the development of innovative preventive and therapeutic approaches. Trial: NCT04750980.

Fungal sensitization and positive fungal culture from sputum in children with asthma are associated with reduced lung function and acute asthma attacks respectively.

BACKGROUND: Sensitization to thermotolerant fungi, including filamentous fungi and Candida albicans, is associated with poor lung function in adults with severe asthma. Data in children are lacking. Environmental exposure to fungi is linked with acute severe asthma attacks, but there are few studies reporting the presence of fungi in the airways during asthma attacks. METHODS: We investigated the association between fungal sensitization and/or positive fungal sputum culture and markers of asthma severity in children with chronic and acute asthma. Sensitization was determined using serum-specific IgE and skin prick testing against a panel of five fungi. Fungal culture was focused towards detection of filamentous fungi from sputum samples. RESULTS: We obtained sensitization data and/or sputum from 175 children: 99 with chronic asthma, 39 with acute asthma and 37 controls. 34.1% of children with chronic asthma were sensitized to thermotolerant fungi compared with no children without asthma (p =< 0.001). These children had worse pre-bronchodilator lung function compared with asthmatics without sensitization including a lower FEV1 /FVC ratio (p < .05). The isolation rate of filamentous fungi from sputum was higher in children with acute compared with chronic asthma. CONCLUSIONS: Fungal sensitization is a feature of children with chronic asthma. Children sensitized to thermotolerant fungi have worse lung function, require more courses of systemic corticosteroids and have greater limitation of activities due to asthma. Asthma attacks in children were associated with the presence of filamentous fungi positive sputum culture. Mechanistic studies are required to establish whether fungi contribute directly to the development of acute asthma.

Perceived Versus Actual Aeroallergen Sensitization in Urban Children.

BACKGROUND: Individuals often report allergy to specific aeroallergens, but allergy testing can reveal disparate sensitization. OBJECTIVE: To characterize the agreement between perceived and actual sensitization to individual aeroallergens in an urban pediatric population. METHODS: A total of 253 children were enrolled from pediatric clinics in New York, NY. Detailed questionnaires regarding perceived sensitization and serum specific IgE measurements to 10 common aeroallergens were completed. Agreement between perceived and actual sensitization (sIgE ≥ 0.35 kUA/L) to individual aeroallergens was assessed by Cohen's kappa. Multivariable logistic regression models adjusted for potential confounders were used to test for associations between perceived and actual sensitization. RESULTS: A total of 161 (63.6%) of 253 children reported perceived sensitization to 1 or more aeroallergen, and 203 (80.2%) were actually sensitized to 1 or more aeroallergen. Agreement between perceived and actual aeroallergen sensitization was fair for most aeroallergens, with greatest agreement for cat dander (κ, 0.42; 95% CI, 0.32-0.53) and dust (κ, 0.32; 95% CI, 0.20-0.44). Models adjusted for potential confounders showed nearly 6-fold odds of sensitization to cat dander given perceived cat allergy (adjusted odds ratio, 5.82; 95% CI, 2.91-11.64), and over 2-fold odds of sensitization to Dermatophagoides pteronyssinus, Dermatophagoides farinae, dog dander, or grass pollen given perceived sensitization to their respective allergens. Among children with no perceived sensitization, actual sensitization ranged from 5.4% to 30.4%, and was more common for indoor versus outdoor allergens, including cockroach. CONCLUSIONS: Children who perceive allergen sensitization to cat, dog, dust, or grass are likely to demonstrate actual sensitization to these individual allergens. Children with no perceived sensitization to allergens are nonetheless frequently sensitized.

Geographic and demographic variations of inhalant allergen sensitization in Koreans and non-Koreans.

BACKGROUND: To diagnose and treat respiratory allergic diseases, it is important to identify the specific allergens involved. Many differences exist between common inhalant allergens depending on the residential environment and demographic factors. This study aimed to compare common inhalant allergens between Koreans and non-Koreans according to their residential region, age, and sex. METHODS: This study evaluated 15,334 individuals who underwent serum tests for multiple allergen-specific immunoglobulin E at a tertiary academic medical center between January 2010 and December 2016. The individuals included 14,786 Koreans and 548 non-Koreans. The AdvanSure™ Allostation assay (LG Life Science, Korea) was used to test for 33 inhalant allergens. RESULTS: The house dust mite (HDM) was the most common allergen in both Koreans and non-Koreans, although the proportion of individuals with HDM sensitization was greater among Koreans. High sensitization rates for various pollen types were detected among Koreans in Gangwon region, whereas Japanese cedar pollen was unique among Koreans in Jeju region. Grass pollen and animal dander were relatively common among individuals from the Americas, whereas weed and grass pollen accounted for the 10 most common allergens for individuals from Central Asia. The total sensitization rate, sensitization to HDM, and sensitization to animal dander peaked among adolescents and young adults, then subsequently decreased with age. CONCLUSIONS: This large-scale study demonstrates that various regional and age-related differences exist in the allergen sensitization rates of Koreans and non-Koreans. These data could be useful for development of avoidance measures, immunotherapy for causative allergens, and policymaking regarding allergic diseases.

Comparison of Singleplex Specific IgE Detection Immunoassays: ImmunoCAP Phadia 250 and Immulite 2000 3gAllergy.

BACKGROUND: The identification of clinically meaningful specific immunoglobulin E (sIgE) is important for the diagnosis and management of allergic diseases. Various in vitro sIgE detection methods are available worldwide. Depending on the number of antigens that can be tested simultaneously, there are two representative methods: singleplex and multiplex. Singleplex sIgE detection is mainly provided by Thermo Fisher (ImmunoCAP) and Siemens (Immulite). This study aimed to compare the diagnostic agreement of two singleplex sIgE detection assays. METHODS: Sera from 209 Korean patients with allergic disease were used to compare the ImmunoCAP and Immulite assays with respect to the following allergens: inhalant allergens (Dermatophagoides farinae, cat and dog dander, oak, rye grass, mugwort, Alternaria, German cockroach) and food allergens (hen's egg white, cow's milk, wheat, peanut, soybean, and shrimp). Data from 902 paired comparison tests were included for comparisons. Qualitative, semi-quantitative, and quantitative comparisons were performed using statistical analyses. RESULTS: In qualitative comparisons, the positivity and negativity agreements ranged from 75% (wheat, shrimp) to 96% (Alternaria). Class consistency (classes 0-6) was well matched. Spearman's rank correlation coefficients for all allergens except shrimp were over 0.7. In quantitative comparisons, all allergens excluding shrimp showed >0.7 intra-class correlation coefficients. CONCLUSIONS: The ImmunoCAP and Immulite systems showed similar performances. However, clinicians should consider fundamental methodological differences between the assays.

Aeroallergens, atopy and allergic rhinitis in the Middle East.

The literature on the nature and prevalence of indoor and/or outdoor aeroallergens, atopy and symptoms of rhinitis and asthma in the Middle East region (defined here as Bahrain, Egypt, Iran, Iraq, Israel, Jordan, Kuwait, Lebanon, Oman, Palestine, Qatar, Kingdom of Saudi Arabia - KSA, Syria, United Arab Emirates and Yemen) was reviewed. Although documentation was poor in all countries other than Iran and the KSA, a wide range of "global" and "local" aeroallergens (grass, weed and tree pollens, fungal spores, insect allergens, dander, and house dust mites) has been observed across the region. The prevalence of current self-reported or parent-reported symptoms of rhinitis ranged from 9% to 38%. Researchers have suggested that the high atopy rates and self-reported rhinitis rates are associated with an on-going shift towards a "western" lifestyle.

Myeloid differentiation protein 2 facilitates pollen- and cat dander-induced innate and allergic airway inflammation.

BACKGROUND: The National Health and Nutrition Examination Survey identified several pollens and cat dander as among the most common allergens that induce allergic sensitization and allergic diseases. We recently reported that ragweed pollen extract (RWPE) requires Toll-like receptor 4 (TLR4) to stimulate CXCL-mediated innate neutrophilic inflammation, which in turn facilitates allergic sensitization and airway inflammation. Myeloid differentiation protein 2 (MD2) is a TLR4 coreceptor, but its role in pollen- and cat dander-induced innate and allergic inflammation has not been critically evaluated. OBJECTIVE: We sought to elucidate the role of MD2 in inducing pollen- and cat dander-induced innate and allergic airway inflammation. METHODS: TCM(Null) (TLR4(Null), CD14(Null), MD2(Null)), TLR4(Hi), and TCM(Hi) cells and human bronchial epithelial cells with small interfering RNA-induced downregulation of MD2 were stimulated with RWPE, other pollen allergic extracts, or cat dander extract (CDE), and activation of nuclear factor κB (NF-κB), secretion of the NF-κB-dependent CXCL8, or both were quantified. Wild-type mice or mice with small interfering RNA knockdown of lung MD2 were challenged intranasally with RWPE or CDE, and innate and allergic inflammation was quantified. RESULTS: RWPE stimulated MD2-dependent NF-κB activation and CXCL secretion. Likewise, Bermuda, rye, timothy, pigweed, Russian thistle, cottonwood, walnut, and CDE stimulated MD2-dependent CXCL secretion. RWPE and CDE challenge induced MD2-dependent and CD14-independent innate neutrophil recruitment. RWPE induced MD2-dependent allergic sensitization and airway inflammation. CONCLUSIONS: MD2 plays an important role in induction of allergic sensitization to cat dander and common pollens relevant to human allergic diseases.

Cross allergic reactions in infants and toddlers with atopic dermatitis.

PURPOSE: Prevalence and clinical significance of cross sensitization in children up to 3 years old, diagnosed with atopic dermatitis. MATERIAL AND METHOD: The retrospective study included 69 children up to 3 years old with atopic dermatitis. Allergological diagnostics was performed based on skin tests, determination of total IgE concentration and allergen-specific IgE. RESULTS: Cross sensitization was found in 26% of children. Other patients were qualified to the control group. The sensitization to trees pollen and fruits as well as grass pollen and vegetables were the most frequent types of cross allergy. The patient's family history was positive with regard to atopy in 72% of children from the study group vs. 31% of children from the control group. The statistically higher prevalence of allergic rhinitis and bronchial asthma as well as co-existence of sensitization to house dust mite and animal dander were revealed in the study group. The total concentration of IgE, eosinophilia and SCORAD values were statistically higher in the study group. Children with cross sensitization required systemic steroid therapy more frequently. CONCLUSION: In children up to 3 years with atopic dermatitis and sensitization to plant pollen, the role of a pollen-food allergy syndrome must be taken into account in the pathogenesis of the disease. In children with cross sensitization, the course of atopic dermatitis is more severe; the symptoms from the respiratory and digestive system co-exist. The positive family history is a factor, predisposing to the development of cross sensitization in infants and toddlers.