BACKGROUND: There are marked sex differences in the prevalence and severity of asthma, both during childhood and adulthood. There is a relative lack of comprehensive studies exploring sexdifferences in pediatric asthma cohorts.
OBJECTIVE: To identify the most relevant sex differences in sociodemographic, clinical, and laboratory variables in a well-characterized large pediatric asthma cohort.
METHODS: We performed a cross-sectional analysis of the Mayo Clinic Olmsted County Birth Cohort. In the full birth cohort, we used a natural language-processing algorithm based on the Predetermined Asthma Criteria for asthma ascertainment. In a stratified random sample of 300 children, we obtained additional pulmonary function tests and laboratory data. We identified the significant sex differences among available sociodemographic, clinical, and laboratory variables.
RESULTS: Boys were more frequently diagnosed with having asthma than girls and were younger at the time of asthma diagnosis. There were no sex differences in relation to socioeconomic status. We identified a male predominance in the presence of a tympanostomy tube and a female predominance in the history of pneumonia. A higher percentage of boys had a forced expiratory volume in 1 second/forced vital capacity ratio less than 0.85. Blood eosinophilia and atopic sensitization were also more common in boys. Finally, boys had higher levels of serum periostin than girls.
CONCLUSIONS: This study described significant sex differences in a large pediatric asthma cohort. Overall, boys had earlier and more severe asthma than girls. Differences in blood eosinophilia and serum periostin provide insights into possible mechanisms of the sex bias in childhood asthma.

Inorganic elements are added to toys as impurities to give desired stability, brightness, flexibility, and color; however, these elements may cause numerous health issues after acute or chronic exposure. In this study, the inorganic profile of 14 elements (Al, As, Ba, Cd, Co, Cr, Cu, Hg, Mn, Ni, Se, Sb, Pb, and Zn) in 63 toy makeup products was identified by inductively coupled plasma-mass spectrometry after microwave acid digestion method. Additionally, organic allergen fragrance was investigated by gas chromatography-mass spectrometry. The systemic exposure dosage (SED), margin of safety (MoS), lifetime cancer risk (LCR), hazard quotient (HQ), and hazard indices were used to assess the safety evaluation. Then, 57 out of 63 samples (90.48%) exceeded the limits at least for one toxic element with descending order Ni > Cr > Co > Pb > Sb > Cd > As > Hg. The SED values were compared with tolerable daily intake values and remarkably differences were found for Al and Pb. The MoS values for 57.15% of samples exceeded the limit value for Al, As, Cd, Co, Hg, Mn, Sb, and Zn elements. The LCR values were observed at 100% (n = 63), 79.37% (n = 50), 85.71% (n = 54), 77.78% (n = 49), and 18.87% (n = 10) for Cr, Ni, As, Pb, and Cd, respectively. Also, the skin sensitization risks were obtained for Cr and Ni at 26.980% (n = 17) and 9.52% (n = 6), respectively. The HQ values for 80% of samples were found to be ≥ 1 at least for one parameter. The investigation of fragrance allergens in samples did not show any significant ingredients. As a result, toy makeup products marketed in local stores were found to be predominantly unsafe. Children should be protected from harmful chemicals by regular monitoring and strict measures.

OBJECTIVE: This study aimed to identify by in silico methods tropomyosin consensus B and T epitopes of shrimp species, house dust mites, insects, and nematodes associated with allergic diseases in tropical countries.
METHODS: In silico analysis included tropomyosin from mites (Der p 10, Der f 10, Blo t 10), insects (Aed a 10, Per a 7, Bla g 7), shrimp (Lit v 1, Pen m 1, Pen a 1), and nematode (Asc l 3) all sequences were taken from the UniProt database. Linear IgE epitopes were predicted with AlgPred 2.0 and validated with BepiPred 3.0. MHC-II binding T cell epitopes were predicted using the IEDB server, which implements nine predictive methods (consensus method, combinatorial library, NN-align-2.3, NN- align-2.2, SMM-align, Sturniolo, NetMHCIIpan 3.1, and NetMHCIIpan 3.2) these predictions focused on 10 HLA-DR and 2 HLA-DQ alleles associated with allergic diseases. Subsequently, consensus B and T epitopes present in all species were identified.
RESULTS: We identified 12 sequences that behaved as IgE-epitopes and B-cell epitopes, three of them: 160RKYDEVARKLAMVEA174, 192ELEEELRVVGNNLKSLEVSEEKAN215, 251KEVDRLEDELV261 were consensus in all species. Eleven peptides (T-epitopes) showed strong binding (percentile rank ≤ 2.0) to HLA-DRB1*0301, *0402, *0411, *0701, *1101, *1401, HLA-DQA1*03:01/DQB1*03:02, and HLA- DQA1*05:01/DQB1*02:01. Only two T-epitopes were consensus in all species: 167RKLAMVEADLERAEERAEt GEsKIVELEEELRV199, and 218EEeY KQQIKT LTaKLKEAEARAEFAERSV246. Subsequently, we identified 2 B and T epitope sequences and reached a consensus between species 167RKLAMVEA174 and 192ELEEELRV199.
CONCLUSIONS: These data describe three sequences that may explain the IgE cross-reactivity between the analyzed species. In addition, the consensus B and T epitopes can be used for further in vitro investigations and may help to design multiple-epitope protein-based immunotherapy for tropomyosin-related allergic diseases.
OBJECTIVE: Este estudio tuvo como objetivo identificar mediante métodos in silico epítopes B y T consenso de tropomiosina de especies de camarón, ácaros del polvo doméstico, insectos y nematodos asociados a enfermedades alérgicas en países tropicales.
UNASSIGNED: El análisis in silico incluyó tropomiosina de ácaros (Der p 10, Der f 10, Blo t 10), insectos (Aed a 10, Per a 7, Bla g 7), camarones (Lit v 1, Pen m 1, Pen a 1), y nematodo (Asc l 3). Todas las secuencias se tomaron de la base de datos UniProt. Los epítopes IgE lineales se predijeron con AlgPred 2.0 y se validaron con BepiPred 3.0. Los epítopes de células T de unión a MHC-II se predijeron utilizando el servidor IEDB, que implementa nueve métodos predictivos (método de consenso, biblioteca combinatoria, NN-align-2.3, NN-align-2.2, SMM-align, Sturniolo, NetMHCIIpan 3.1 y NetMHCIIpan 3.2). Estas predicciones se centraron en diez alelos HLA-DR y 2 HLA-DQ asociados con enfermedades alérgicas. Posteriormente, se identificaron epítopes consenso B y T presentes en todas las especies.
RESULTS: Se identificaron 12 secuencias que se comportaron como epítopes de IgE y, también, como epítopes de células B. Tres de ellas: 160RKYDEVARKLAMVEA174, 192ELEEELRVVGNNLKSLEVSEEKAN213 y 251KEVDRLEDELV261, fueron consenso en todas las especies. Once péptidos mostraron una fuerte unión (rango percentil ≤ 2,0) a HLA-DRB1*0301, *0402, *0411, *0701, *1101, *1401 y a HLA HLA-DQA1*03:01/DQB1*03:02, o HLA-DQA1*05:01/DQB1*02:01. Solo se encontraron dos secuencias: 167RKLAMVEADLERAEERAEtGEsKIVELEEELRV199 con fuerte afinidad por HLA-DQA1*03:01/DQB1*03:02, y HLA-DQA1*05:01/DQB1*02:01. Se identificaron dos secuencias que son epítopos B y T, y son consenso entre especies: 167RKLAMVEA174 y 192ELEEELRV199.
CONCLUSIONS: Estos datos describen tres secuencias que pueden explicar la reactividad cruzada de IgE entre las especies analizadas. Además, los epítopos B y T consenso se pueden usar para investigaciones in vitro adicionales, y pueden ayudar a diseñar inmunoterapia basada en proteínas de múltiepítopes para enfermedades alérgicas relacionadas con la tropomiosina.

Tropomyosin (TM) is a pan-allergen with cross-reactivity to arthropods, insects, and nematodes in tropical regions. While IgE epitopes of TM contribute to sensitization, T-cell (MHC-II) epitopes polarize the Th2 immune response. This study aimed to identify linear B and T consensus epitopes among house dust mites, cockroaches, Ascaris lumbricoides, shrimp, and mosquitoes, exploring the molecular basis of cross-reactivity in allergic diseases. Amino acid sequences of Der p 10, Der f 10, Blo t 10, Lit v 1, Pen a 1, Pen m 1, rAsc l 3, Per a 7, Bla g 7, and Aed a 10 were collected from Allergen Nomenclature and UniProt. B epitopes were predicted using AlgPred 2.0 and BepiPred 3.0. T epitopes were predicted with NetMHCIIpan 4.1 against 10 HLA-II alleles. Consensus epitopes were obtained through analysis and Epitope Cluster Analysis in the Immune Epitope Database. We found 7 B-cell epitopes and 28 linear T-cell epitopes binding to MHC II. A unique peptide (residues 160-174) exhibited overlap between linear B-cell and T-cell epitopes, highly conserved across tropomyosin sequences. These findings shed light on IgE cross-reactivity among the tested species. The described immuno-informatics pipeline and epitopes can inform in vitro research and guide synthetic multi-epitope proteins\' design for potential allergology immunotherapies. Further in silico studies are warranted to confirm epitope accuracy and guide future experimental protocols.

Allergic Rhinitis (AR) is rising in incidence in both developed and developing countries. Genetics and epigenetics have a potential role to play. The pattern and severity of AR have implications with regard to choice of treatment, which itself could be related to patient specific genetic and epigenetic factors. Hence, the present study was undertaken to correlate the patient characteristics with AR pattern and severity, in order to understand the pathophysiology of AR. The study also aimed to find out the allergen sensitivity pattern among patients attending a tertiary care centre of rural central India, where climatic variations make it a high prevalence zone. Prospective Observational study on 90 patients with clinically diagnosed Allergic Rhinitis confirmed by Skin Prick Tests. Patient characteristics like demographic data, data relevant to allergen exposure, occupation, family history of atopy and gender; and Disease characteristics like severity (mild, mod-severe), pattern (continuous/ intermittent), type of disease (seasonal/perennial) were noted, analysed and correlation studied. Majority of the patients with AR were in the age group of 15-40 years. Medical students (52%) suffered from moderate to severe type of Allergic Rhinitis, with Persistent disease in approximately 80%. Similarly, 70.59% of farmers had moderate to severe type of the disease, with persistent disease in 70%. In the present study, in clinically diagnosed allergic rhinitis patients, Mite was the commonest allergen found on Skin Prick Test overall and in Medical students, whereas Pollen sensitivity was more common among farmers. 56.66% of the patients had negative family history of atopy. Severity and type of AR depend on allergen exposure. In farmers and medical professionals, persistent and moderate to severe type of disease was more common, as they were persistently exposed to different type of allergens, mites in case of medical professionals and pollens in farmers. Hence, the Disease characteristics, as defined by ARIA guidelines, should not be taken in isolation and management should consider the Patient characteristics for deciding and devising protocols. In the present study, more than 50% patients were without family history of atopy. Hence, the role of various environmental factors, leading to epigenetic changes could be a major contributor in the increase in incidence of allergic rhinitis in recent times. Occurrence of perennial moderate to severe form of disease, in majority of farmers, defies the phenomenon of \"Hygiene Hypothesis\", focusing on the role of epigenetic changes and various outdoor allergens in the development of allergic rhinitis in them.

BACKGROUND: Component-resolved diagnosis (CRD) has been decisive in exploring the mechanisms of IgE sensitization, but the predictive ability to detect asthma has not been addressed. We aim to develop and evaluate the performance of a personalized predictive algorithm for asthma that integrates information on allergic sensitization using CRD.
METHODS: One thousand one hundred one twenty-five children from the Generation XXI birth cohort were randomly selected to perform a screening test for allergic sensitization and a subsample was characterized using CRD against 112 allergen components. Allergen components were analyzed using volcano plots and partial least squares (PLS) analysis. Logistic regression was performed to assess the associations between the obtained latent components (LC) and allergic outcomes (asthma, rhinitis, eczema) including other potential predictors used in previous asthma risk scores. The accuracy of the model in predicting asthma was assessed using Receiver Operating Characteristic (ROC) curve statistics.
RESULTS: In the PLS, the first LC was positively associated with asthma, rhinitis, and eczema. This LC was mainly driven by positive weights for Der p 1/2/23, Der f 1/2, and Fel d 1. The main components in the second LC were pollen and food allergens. History of early wheezing and parental allergy were included in the predictive model and the area under the curve improved to 0.82.
CONCLUSIONS: This is the first approach to improve the clinical applicability of CRD by combining CRD and clinical data to predict asthma at 13 years. Sensitization to distinct allergen molecules seems relevant to improve the accuracy of asthma prediction models.

Responding to international research showing that early introduction of common food allergens can reduce the chance of developing allergies, in 2016 the Australasian Society of Clinical Immunology and Allergy (ASCIA) revised allergen introduction guidelines, recommending earlier introduction of allergens to infants in their first year. Australia has high food allergy rates, and limited understanding of adherence to allergen introduction guidelines, especially in rural areas. This project explored rural parent adherence to ASCIA guidelines.
This was a mixed method cross sectional study using an online survey including multiple-choice and qualitative short answer responses. The sample were 336 women from two rural health districts in New South Wales. All were aged 18 or over, and either pregnant or had delivered a baby since July 2018. Descriptive statistics were used to measure behavioural alignment with the recommended guidelines, thematic analysis was used to analyse attitudes and explanations.
In 84.3% of children, feeding adhered to all four guidelines studied, including no elimination of allergens during pregnancy (98%), age of introduction of solids (97.7%), continuation of breast milk/cow\'s milk formula during introduction of solids (95%), and age of introduction of allergens (92.9%). Adherence was not significantly correlated with the education (X2 = 17.9, P = .056), prior history of allergy [neither mother (X2 = 0.945,P = .623) nor previous children (X2 = 0.401,P = .818)], or primary care received during pregnancy. More than 90% of participants agreed or strongly agreed that the guidelines are realistic, trustworthy, and important for the health of their child. However, thematic analysis revealed that parents\' perceptions of a child\'s individual progress, and medical conditions or other circumstances, such as challenges with breastfeeding, will often take precedence over adherence to specific guideline recommendations.
High rates of adherence with ASCIA guidelines found here are comparable with findings from metropolitan studies and encouraging for future population health. Participant comments on the guidelines imply to rural policymakers that there are multiple influences on parent decisions about infant feeding, often including parents\' own intuition and experiences. Further studies to improve understanding of the role of information, carers, and other influences on parent decision-making concerning feeding attitudes and behaviours will be necessary to optimise adherence in rural areas.

To determine the prevalence of sensitivity to common inhaled and food allergens among children with allergic rhinitis (AR) in Changzhou in eastern China and provide a basis for epidemiological research of pediatric allergic rhinitis and allergen avoidance in this region.
This was a retrospective observational study, a total of 1248 children with AR were enrolled at the Third People\'s Hospital of Changzhou between January 2018 and December 2019. The serum-specific immunoglobulin E (sIgE) to 19 kinds of inhaled and food allergens and serum total IgE were detected with the AllergyScreen test (Mediwiss Analytic GmbH, Moers, Germany). All participants had a positive reaction to at least one allergen in the test (the sIgE concentration ≥ 0.35 IU/ml).
Among the patients, 818 (65.54%) were male and 430 (34.46%) were female, with 81 (6.50%) aged 1-3 year, 501 (40.14%) aged 4-7 year, and 666 (53.36%) aged 8-14 year. The positivity rate of inhaled allergens was 80.05% (n = 999), while the positivity rate of food allergens was 66.19% (n = 826). 828 patients (66.35%) were sensitized to multiple allergens. The most common inhaled allergens were Dermatophagoides pteronyssinus (65.38%), mold mix (25.56%), house dust (20.67%), and dog hair dander (13.94%), and the most common food allergens were cow\'s milk (30.31%), cashew nut (27.9%), egg (22.68%), and beef (12.98%). With an increase in age, the inhaled allergen positivity rate showed a significant increase (P < 0.01), while the food allergen positivity rate decreased significantly (P < 0.01). There were significant age differences in total IgE levels (P < 0.01) and the total IgE level was highest in the group aged 8-14 year.
Dermatophagoides pteronyssinus was the most common sensitizing allergen in pediatric patients with AR in Changzhou. Several other inhaled and food allergens were also common. We observed that multiple allergenic factors play an important role in the occurrence and development of AR.

BACKGROUND: Environmental co-exposure to allergen and traffic-related air pollution is common globally and contributes to the exacerbation of respiratory diseases. Individual responses to environmental insults remain variable due to gene-environment interactions.
OBJECTIVE: This study examined whether single nucleotide polymorphisms (SNPs) in lung cell surface receptor genes modifies lung function change and immune cell recruitment in allergen-sensitized individuals exposed to diesel exhaust (DE) and allergen.
METHODS: In this randomized, double-blinded, four-arm, crossover study, 13 allergen-sensitized participants underwent allergen inhalation challenge following a 2-hour exposure to DE, particle-depleted diesel exhaust (PDDE) or filtered air (FA). Lung function tests and bronchoscopic sample collection were performed up to 48 h after exposures. Transient receptor potential channel (TRPA1 and TRPV1) and toll-like receptor (TLR2 and TLR4) risk alleles were used to construct an unweighted genetic risk score (GRS). Exposure-by-GRS interactions were tested using mixed-effects models.
RESULTS: In participants with high GRS, allergen exposure was associated with an increase in airway hyperresponsiveness (AHR) when co-exposed to PDDE (p = 0.03) but not FA or DE. FA and PDDE also were associated with a relative increase in macrophages and decrease in lymphocytes in bronchoalveolar lavage.
CONCLUSIONS: TRPs and TLRs variants are associated with increased AHR and altered immune cellularity in allergen-exposed individuals. This effect is blunted by DE exposure, suggesting greater influence of unmeasured gene variants as primary meditators of a particulate-rich co-exposure.
BACKGROUND: The study was registered with ClinicalTrials.gov on December 20, 2013 (NCT02017431).

Pediatric allergic rhinoconjunctivitis has become a public concern with an increasing incidence year by year. Conventional subcutaneous immunotherapy (SCIT) has long treatment time, high cost and poor compliance. The novel immunotherapy significantly shortens the course of treatment by directly injecting allergens into cervical lymph nodes, which can perform faster clinical benefits to children.
By comparing with SCIT, this study aimed to evaluate the long-term efficacy and safety of intra-cervical lymphatic immunotherapy (ICLIT).
This is a prospective randomized controlled study. A total of 50 allergic rhinoconjunctivitis children with dust mite allergy was randomly divided into ICLIT group and SCIT group, receiving three cervical intralymphatic injections of dust mite allergen or three years of subcutaneous injection, separately. Primary outcomes included total nasal symptom scores (TNSS), total ocular symptom scores (TOSS), total symptom scores (TSS), total medication scores (TMS), and total quality of life score. Secondary outcomes included pain perception and adverse reactions during treatment. Other secondary outcome was change in Dermatophagoides pteronyssinus (Derp) and Dermatophagoides farina (Derf) -specific IgE level.
Both groups had significantly decreased TNSS, TOSS, TSS, TMS, and total quality of life score after 36 months of treatment (p<0.0001). Compared with SCIT, ICLIT could rapidly improve allergic symptoms (p<0.0001). The short-term efficacy was consistent between the two groups (p=0.07), while the long-term efficacy was better in SCIT group (p<0.0001). The pain perception in ICLIT group was lower than that in SCIT group (p<0.0001). ICLIT group was safer. Specifically, the children had only 3 mild local adverse reactions without systemic adverse reactions. The SCIT group had 14 systemic adverse reactions. At last, the serum Derp and Derf-specific IgE levels in ICLIT and SCIT groups decreased 3 years later (p<0.0001).
ICLIT could ameliorate significantly the allergic symptoms in pediatric patients with an advantage in effectiveness and safety, besides an improved life quality including shortened period of treatment, frequency of drug use and pain perception.
https://www.chictr.org.cn/, identifier ChiCTR1800017130.