Mite allergen sensitization patterns in Turkish children: Age-related changes and molecular correlations.

BACKGROUND: Mites are ubiquitous aeroallergens found worldwide. Elucidating individual mite allergen sensitization patterns provides critical insights for managing allergic diseases. This study aimed to investigate molecular allergen (MA) sensitization patterns across different age groups and explore cluster relationships among mite-sensitized children. METHODS: We analyzed 76 children who exhibited sensitization to at least one of the 17 distinct mite MAs through microarray testing. RESULTS: Dermatophagoides farinae exhibited a slightly higher prevalence of sensitization compared with Dermatophagoides pteronyssinus. Der p 1/2 and Der f 1/2 demonstrated an almost 40% sensitization rate, while Der p 10/Blo t 10, Der p 20, Der p 23, and Gly d 2/Lep d 2 displayed an approximately 20% sensitization rate. Sensitization levels and ratios increased significantly with age for Der p 23 but showed numerical rises for other MAs, except for Der p 10/Blo t 10. The presence of various types of atopic diseases had only a minimal impact on sensitization profiles. Strong correlations emerged between Der f 2 and Der p 2, Der p 10 and Blo t 10, Der p 21 and Blo t 5, as well as Gly d 2 and Lep d 2. Hierarchical cluster analysis substantiated these relationships. Der p 10 and its homolog Blo t 10-sensitive patients (15/76) were mostly seen as mono sensitization(12/15). Ten patients exhibited monosensitization to Der p 20, suggesting a possible association with scabies infection. CONCLUSION: In children, mite sensitization diversity and levels increased with age. The presence of significant correlations/cluster relationships among these sensitizations underscores homologies among specific MAs.

Prevalence of aeroallergen sensitization in children in Northern China.

OBJECTIVE: This study aimed to analyze the sensitization rate of different aeroallergens in children of different age, sex, and disease groups, describe the changing trend of different aeroallergens in different ages, and analyze the sensitization risk factors for asthma. METHODS: Children (<18 years old) with suspected atopic diseases who visited the Department of Allergy of Children's Hospital Affiliated to Capital Institute of Pediatrics and underwent a skin prick test (SPT) were retrospectively enrolled from January 2019 to November 2021. RESULTS: A total of 5465 patients (3514 boys, 1951 girls; mean age, 7 ± 3 years) were enrolled. Of them, 3703 patients (67.8%) were sensitized to at least one aeroallergen. Before 4 years of age, mold was the most prevalent aeroallergen (103/380 [27.1%]), whereas after 4 years of age, weed pollen was the most prevalent aeroallergen. After 6 years of age, tree pollen became the second most prevalent aeroallergen. After 12 years of age, the sensitization rate of indoor aeroallergens was lower than that of outdoor aeroallergens. Logistic regression showed that sensitization to mold (odds ratio [OR]:1.4, 95% confidence interval (CI): 1.2-1.7, p < 0.001), animal dander (OR: 1.6, 95% CI: 1.4-1.9, p < 0.001), and polysensitization (OR: 1.4, 95% CI: 1.0-1.8, p = 0.038) were potential sensitization risk factors for asthma. CONCLUSIONS: Mold is an important allergen in early life. Different kinds of allergens affect different age groups. Patients who are sensitized to mold or animal dander or experience polysensitization should be carefully monitored for asthma risk.

Allergen immunotherapy for atopic dermatitis: Systematic review and meta-analysis of benefits and harms.

BACKGROUND: Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and microbes. The role of environmental allergens (aeroallergens) in triggering AD remains unclear. OBJECTIVE: We systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD. METHODS: As part of the 2022 American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters AD Guideline update, we searched the MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Global Resource for Eczema Trials, and Web of Science databases from inception to December 2021 for randomized controlled trials comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard care) for guideline panel-defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares, and adverse events. Raters independently screened, extracted data, and assessed risk of bias in duplicate. We synthesized intervention effects using frequentist and Bayesian random-effects models. The GRADE approach determined the quality of evidence. RESULTS: Twenty-three randomized controlled trials including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on SCIT and SLIT have similar relative and absolute effects and likely result in important improvements in AD severity, defined as a 50% reduction in SCORing Atopic Dermatitis (risk ratio [95% confidence interval] 1.53 [1.31-1.78]; 26% vs 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index by 4 points or more (risk ratio [95% confidence interval] 1.44 [1.03-2.01]; 39% vs 56%, absolute difference 17%; both outcomes moderate certainty). Both routes of AIT increased adverse events (risk ratio [95% confidence interval] 1.61 [1.44-1.79]; 66% with SCIT vs 41% with placebo; 13% with SLIT vs 8% with placebo; high certainty). AIT's effect on sleep disturbance and eczema flares was very uncertain. Subgroup and sensitivity analyses were consistent with the main findings. CONCLUSIONS: SCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL. SCIT increases adverse effects more than SLIT. These findings support a multidisciplinary and shared decision-making approach to optimally managing AD.

Outdoor Alternaria and Cladosporium spores and acute asthma.

BACKGROUND: Outdoor Alternaria and Cladosporium spores are ubiquitous. Few studies have assessed their impact on asthma hospitalizations providing conflicting results, mainly focused on vulnerable paediatric populations. We aimed to study the impact of outdoor Alternaria and Cladosporium concentrations on acute hospitalizations in the Capital Region of Denmark. METHODS: This is a bi-directional case-crossover study with 26 years of national registry data at individual level on acute asthma hospitalizations and daily average data on Alternaria and Cladosporium, pollen (Artemisia, Poaceae), maximal temperature, and air pollution. Conditional logistic regression models were applied to assess the associations. Concentration quartiles at lag 0 were used for categorizing the exposure. RESULTS: For lags 0-2, the odds of hospitalization were significantly higher for both Alternaria and Cladosporium at concentration quartile 2-4 compared with quartile 1. When stratified for age and sex, odds of hospitalization at Alternaria quartiles 2-4 were significantly higher in males below 40 years at lag 0-2, and at lag 0 in females (18-30 years), while quartiles 2-4 of Cladosporium concentrations were associated with significantly higher odds in boys (0-17 years) at lag 1-3, males (18-39 years) at lag 0-1, females (18-39 years) at lag 1-2, males (40-64 years) at lag 0-2, females (40-64 years) at lag 0 and 2, in seniors (65+ years) male at lag 1-2 and female at lag 0-1. The effect of Alternaria varied significantly depending on the level of Cladosporium (p < .0001). CONCLUSION: Ambient Alternaria and Cladosporium spores can induce asthma hospitalizations. Males are more susceptible to both genera. Males and females under age 40 years are more susceptible to Alternaria.

Tonsillar transcriptional profiles in atopic and non-atopic subjects.

BACKGROUND: Emerging research suggests that local lymphatic tissue such as tonsils have important role in regulating the immune responses. However, allergen sensitization-induced alterations in transcriptome of tonsils are not known. OBJECTIVES: To examine the key differences in tonsillar gene expression between atopic and non-atopic subjects and further by type of sensitization. METHODS: RNA-sequencing was performed on 52 tonsillar samples from atopic and non-atopic tonsillectomy patients. Sensitization to common food- and aero-allergen was defined by allergen specific IgE. Following groups were studied: (1) aero- and food-allergen sensitized (AS+FS) versus non-sensitized (NS), (2) aeroallergen-sensitized (AS) versus food-allergen sensitized (FS), (3) AS versus NS, (4) FS versus NS. Bioinformatics analysis was done using DESeq2(v3.10.2), WGCNA and GATK pipeline in R software (v3.3.1). Protein-protein interaction network was made from String database. RESULTS: We studied 13 aeroallergen-sensitized, 6 food-allergen sensitized, 4 both food-and aero-allergen-sensitized and 29 non-sensitized tonsillectomy patients. Overall, 697 unique differentially expressed genes (DEGs) were detected in all sensitized subgroups including chemokines (CXCL2, CXCL8, CXCL10, CXCL11), IL-20RA, MUC1 and MUC20. When comparing different groups, the gene expression profiles overlapped except the AS versus FS group comparison, suggesting significantly different gene expression between the two sensitization subgroups. Furthermore, aeroallergen-sensitized subjects had more prominent immune responses compared with non-sensitized and food-allergen sensitized subjects including gene expression for IL-17 pathway and Toll-like receptor signalling pathway. CONCLUSION: Allergic sensitization is associated with extensive tonsillar transcriptomic alterations and changes in immune related genes and pathways. Distinct differences were found between aero-allergen and food-allergen sensitization.

Nasal Provocation Challenges with Aedes aegypti Whole-Body Extract Induces Allergic Rhinitis.

BACKGROUND: Exposure to mosquitoes in the Tropics is perennial, and their somatic and saliva antigens have shown IgE binding capacity, although it is not clear whether this is due to cross-reactivity or primary sensitization. Inhalation of these allergens could trigger an allergic response. OBJECTIVE: The aim of the study was to evaluate the clinical relevance of sensitization to Aedes aegypti in a group of patients with allergic rhinitis. METHODS: A cross-sectional study with allergic rhinitis subjects and healthy controls sensitized to mosquito extract was performed. Sensitization to mosquito and house dust mites was evaluated using skin prick test (SPT) and antibody determination by ELISA. Nasal provocation test (NPT) with whole-body extract was used to determine clinical relevance. RESULTS: Allergic rhinitis patients were more sensitized to mosquito extract than controls with (+) SPT (66.6% vs. 7.6%). From these (+) SPT patients, 44.5% had (+) NPT, and just two (11%) presented mono-sensitization to mosquito. Antibody reactivity was similar between patients and controls; however, (+) NPT patients showed a tendency to had higher levels of IgE and IgG4. DISCUSSION: Mosquitoes are perennial in most tropical areas, and their body allergens could be associated with respiratory allergies.

Evaluation of evidence for interaction between PM2.5 and aeroallergens on childhood asthma exacerbation in Philadelphia, PA, 2011 to 2016.

Fine particulate matter (PM2.5) and aeroallergens (i.e., pollen, molds) are known triggers of asthma exacerbation. Despite mechanistic evidence suggesting synergistic effects between PM2.5 and asthma exacerbation, little epidemiologic work has been performed in children, which has exhibited inconsistency. We conducted a time-series study to explore their interactions using electronic health records (EHR) data in Philadelphia, PA, for asthma diagnoses in outpatient, emergency department [ED], and inpatient settings. Daily asthma exacerbation cases (28,540 asthma exacerbation case encounters) were linked to daily ambient PM2.5 and daily aeroallergen levels during the aeroallergen season of a six-year period (mid-March to October 2011-2016). Asthma exacerbation counts were modeled using quasi-Poisson regression, where PM2.5 and aeroallergens were fitted with distributed lag non-linear functions (lagged from 0 to 14-days), respectively, when modeled as the primary exposure variables. Regression models were adjusted for mean daily temperature/relative humidity, long-term and seasonal trends, day-of-week, and major U.S. holidays. Increasing gradient of RR estimates were observed for only a few primary exposure risk factors [PM2.5 (90th vs. 5th percentile)/aeroallergens (90th percentile vs. 0)], across different levels of effect modifiers. For example, RRs for the association between late-season grass pollen (lag1) and asthma exacerbation were higher at higher levels of PM2.5, 5-days preceding the exacerbation event (low PM2.5: RR = 1.01, 95% CI: 0.93-1.09; medium PM2.5: 1.04, 95% CI: 0.96-1.12; high PM2.5: 1.09, 95% CI: 1.01-1.19). However, most of the highest RRs for aeroallergens were instead observed for days with low- or medium- PM2.5 levels; likewise, when PM2.5 was modeled as the primary exposure with aeroallergens as the effect modifier. Most of the RR estimates did not exhibit gradients that suggested synergism, and were of relatively high imprecision. Overall, our study suggested no evidence for interactions between PM2.5 and aeroallergens in their relationships with childhood asthma exacerbation.

Associations Between Phthalate, Eosinophil, and Aeroallergen Sensitization in Schoolchildren.

BACKGROUND: Phthalates and bisphenol A (BPA) are endocrine-disrupting chemicals and may cause immunological disorders in children. Therefore, according to the region, we investigated urinary phthalates and BPA levels and the relationship between urinary phthalate, aeroallergen sensitization, and eosinophil count during the coronavirus disease 2019 pandemic. METHODS: In total, 203 schoolchildren (134 residential and 69 industrial) aged 7-10 years were enrolled between July 2021 and July 2022. The BPA, metabolites of four high-molecular-weight phthalates (Σ4HMWP) and three low-molecular-weight phthalates (Σ3LMWP), were measured in the urine samples. Total eosinophil count and transepidermal water loss (TEWL) were also measured along with the skin prick test. RESULTS: The two groups had no differences in terms of BPA. The industrial group had significantly more plastic container usage, and there was a difference in the Σ3LMWP (P < 0.001) between the two groups but no difference in the Σ4HMWP (P = 0.234). The quartiles of urinary Σ4HMWP and Σ3LMWP (P < were not associated with the total eosinophil count, vitamin D level, or TEWL. After adjusting for cofactors, the quartiles of urinary Σ4HMWP and Σ3LMWP were significantly associated with total eosinophil count (P < 0.001) but not with aeroallergen sensitization or vitamin D. CONCLUSION: Exposure to phthalates was significantly associated with eosinophil count but not with aeroallergen sensitization or vitamin D. Therefore, reducing the use of plastic containers may effectively prevent exposure to phthalates and reduce Th2 cell-mediated inflammation in children.

The prevalence of sensitization to food allergens in children with atopic dermatitis.

INTRODUCTION: Atopic dermatitis (AD) has a complex pathophysiology. The course of the disease is affected by both environmental factors and allergen hypersensitivities. Food and aeroallergens have a significant role in the pathogenesis and disease control. OBJECTIVE: In this study, it was aimed to determine the prevalence of food and aeroallergen sensitivity of children with AD. METHODS: Children under 18 years with AD who applied to pediatric allergy and immunology outpatient clinics were evaluated. All patients had a skin prick test (SPT) within most common food and aeroallergens. RESULTS: One hundred seventy three patients were studied. Most of the moderate and severe AD patients were boys (boys 64% vs. girls 47%). Symptoms started earlier and positive results in SPTs with food allergens were more common in patients with SCORAD (SCORing Atopic Dermatitis) >25 (p < 0.0001). Egg white (39%), egg yolk (31%), cow's milk (13%) and wheat flour (5%), were the most common allergens, respectively. The SCORAD scores were higher in multiple food sensitized patients' groups (p < 0.001). Although, food sensitizations were prevalent in patients who had higher SCORAD scores (p = 0.001), there was no significant difference in sensitization with aeroallergens. (p = 0.392). CONCLUSION: Sensitizations to both food and aeroallergens are common in patients with AD. In addition, sensitization to these allergens and SCORAD severity in patients with AD have positive correlation.

Food and Aeroallergen Sensitization, Eosinophils Levels and Risk of Atopic Dermatitis in Abuja.

BACKGROUND: The barrier dysfunction of atopic dermatitis (AD) promotes epicutaneous sensitization to aeroallergens. This study aimed to evaluate the prevalence of food and aeroallergen sensitization in AD and to explore the relationship between allergen sensitization and the personal or family history of allergic rhinitis, conjunctivitis, asthma, eosinophil count, and AD severity of Nigerian patients. METHODS: Children and adults with AD who visited the dermatology clinic were included in this study. AD diagnosis was made using the modified Hanifin and Rajka criteria, and severity was rated and graded using the Scoring Atopic Dermatitis (SCORAD) index. Skin-prick test for 14 allergens (5 food and 9 aeroallergens) was used to assess IgE sensitization. To look for significant relationships, chi-square and odds ratio were used. RESULTS: Sensitization to at least one allergen was observed in 65.8% of the patients, sensitization to aeroallergen was 85% and to foods was 15%. More patients had concomitant allergic conjunctivitis (n=29) and only three had asthma. The mean age of onset of AD was 10.6±12.9 years, ranging from 2 months to 51 years, and a family history of atopy was observed in 49.4%. Majority had moderate AD and normal eosinophil count. Allergen sensitization in AD patients was significantly associated with the age of patients but not with personal or family history of allergic rhinitis, conjunctivitis, asthma, eosinophil count or AD severity. CONCLUSION: Analysis of our result showed a high prevalence of food and aeroallergen sensitization in AD. Sensitization was not influenced by the presence of other allergic diseases, eosinophils and the severity of AD.

CONTEXTE: La dysfonction de la barrière cutanée de la dermatite atopique (DA) favorise la sensibilisation épicutanée aux aéroallergènes. Cette étude visait à évaluer la prévalence de la sensibilisation alimentaire et aéroallergénique dans la DA et à explorer la relation entre la sensibilisation aux allergènes et les antécédents personnels ou familiaux de rhinite allergique, conjonctivite, asthme, le taux d'éosinophiles et la sévérité de la DA chez les patients nigérians. MÉTHODES: Les enfants et les adultes atteints de DA qui ont visité la clinique dermatologique ont été inclus dans cette étude. Le diagnostic de la DA a été établi en utilisant les critères modifiés de Hanifin et Rajka, et la gravité a été évaluée et classée à l'aide de l'indice de ScoringAtopic Dermatitis (SCORAD). Le test cutané aux 14 allergènes (5 alimentaires et 9 aéroallergènes) a été utilisé pour évaluer la sensibilisation IgE. Pour rechercher des relations significatives, le chi carré et le rapport de cotes ont été utilisés. RÉSULTATS: Une sensibilisation à au moins un allergène a été observée chez 65,8% des patients, la sensibilisation aux aéroallergènes était de 85% et aux aliments de 15%. Plus de patients présentaient une conjonctivite allergique concomitante (n=29) et seulement trois avaient de l'asthme. L'âge moyen de début de la DA était de 10,6 ± 12,9 ans, allant de 2 mois à 51 ans, et des antécédents familiaux d'atopie ont été observés chez 49,4%. La majorité avait une DAmodérée et un taux d'éosinophiles normal. La sensibilisation aux allergènes chez les patients atteints de DA était significativement associée à l'âge des patients, mais pas aux antécédents personnels ou familiaux de rhinite allergique, conjonctivite, asthme, au taux d'éosinophiles ou à la gravité de la DA. CONCLUSION: L'analyse de nos résultats a montré une prévalence élevée de la sensibilisation alimentaire et aéroallergénique dans la DA. La sensibilisation n'était pas influencée par la présence d'autres maladies allergiques, d'éosinophiles et de la sévérité de la DA. Mots-clés: Dermatite atopique, sensibilisation alimentaire et aéroallergénique, maladies atopiques, éosinophiles, sévérité de la dermatite atopique. Severity of atopic dermatitis Short title:Allergen sensitization in atopic dermatitis.

Cupressus arizonica: an emerging aeroallergen for East Mediterranean children.

Background/aim: Cupressus sempervirens is a tree native to the Mediterranean region. We aimed to investigate the frequency of sensitization/allergy to Cupressus arizonica pollen, which is not native to Anatolia. Materials and methods: Patients aged 5-18 years who underwent respiratory allergy screening in Türkiye's largest referral center over a 1-year period were reviewed retrospectively for a diagnostic study of Cupressus allergy. Results: Of 246 patients, 207 (67.6% male) with a median age of 11.7 (IQR 9.2-15) years were found to be aeroallergen-sensitive and C. arizonica (32%) was the second most common sensitivity after grass pollen (83.6%). In the C. arizonica-sensitive subgroup, only 3% (2/67) were monosensitive, and grass (77.6%), cat (38.8%), and weeds (38.8%) were the most common co-sensitivities. Cup a 1 specific IgE (sIgE) was measured in 26 patients with C. arizonica sensitivity and all were found to be positive. A nasal allergen challenge (NAC) was performed for 44 of 67 patients with C. arizonica sensitivity, and 13 of 44 patients had a positive outcome (NAC+) at the highest two extract concentrations. The Cupressus wheal sizes and Cup a 1 sIgE levels of the NAC+ subgroup were higher than those of the NAC- subgroup but reached significance only for wheal size [6 (5-7.5) vs. 4.5 (4-6), p=0.004]. The NAC+ subgroup reported more frequent nasal discharge, congestion, and eye symptoms than the NAC- subgroup during the relevant pollen season. Conclusion: C. arizonica sensitivity has increased in the East Mediterranean region, similarly to North Mediterranean data, and this is associated with the presence of allergy both clinically and in laboratory findings. C. arizonica should be included in the aeroallergen screening panels of children from the East Mediterranean.

Allergens sensitization among children with allergic diseases in Shanghai, China: age and sex difference.

BACKGROUND: The distribution of allergens has geographic characteristics. Local epidemiological data provides evidence-based strategies for the prevention and management of allergic diseases. Age and sex differences may exist in the prevalence of sensitivity to various allergens. We investigated the distribution of common allergens in allergic children in Shanghai, southeastern China. METHODS: 39,926 children 1 month to 18 years of age diagnosed with allergic diseases were tested for the presence of serum-specific Immunoglobulins E (sIgE) to 17 allergens common to this region, using a reversed enzyme allergosorbent test. RESULTS: 25,757 (64.5%) of the subjects showed elevated sIgE to at least one of the tested allergens. House mite and dust mite were the most common aeroallergens, while egg and milk were the most common food allergens. The most common aeroallergens and food allergens were similar among each allergic disease. By age-group analysis, the positive rates of aeroallergens were higher at older age. Several peaks of sensitization to food allergens were observed in children between 1 and 3 years of age for eggs, milk, nut, crab and shrimp. In addition, the sensitization to beef and mango was highest in children 3-6 years of age. The rate of positive sIgE detection was higher in males than females for all the tested allergens except cockroach, trees and beef. Considering the interplay between sex and ages and other related components (including season, monthly temperature, humidity, air quality index, test rate of patients), the sIgE positive rates of the main aeroallergens increased with age, while the main food allergens decreased; males are more sensitive to several aeroallergens (including dust mite, house mite, cat epithelium, dog epithelium and mulberry). CONCLUSIONS: House mite, dust mite, milk, and egg are major allergens in Shanghai. Children at younger age are more sensitive to food allergens, while increasing overall prevalence of sensitization can be found with increasing age. Boys have higher positive rates of sIgE responses than girls. Knowledge of the prevalence of allergen sensitization in different age groups and sex may help facilitate diagnosis and intervention efforts to mitigate the impact of allergic diseases in this large geographical region. This approach may be extrapolated to other regions.

Large-scale provocation studies identify maladaptive responses to ubiquitous aeroallergens as a correlate of severe allergic rhinoconjunctivitis and asthma.

BACKGROUND: Allergic asthma (AA) and allergic rhinoconjunctivitis (ARC) are common comorbid environmentally triggered diseases. We hypothesized that severe AA/ARC reflects a maladaptive or unrestrained response to ubiquitous aeroallergens. METHODS: We performed provocation studies wherein six separate cohorts of persons (total n = 217) with ARC, with or without AA, were challenged once or more with fixed concentrations of seasonal or perennial aeroallergens in an aeroallergen challenge chamber (ACC). RESULTS: Aeroallergen challenges elicited fully or partially restrained vs. unrestrained evoked symptom responsiveness, corresponding to the resilient and adaptive vs. maladaptive AA/ARC phenotypes, respectively. The maladaptive phenotype was evoked more commonly during challenge with a non-endemic versus endemic seasonal aeroallergen. In an AA cohort, symptom responses evoked after house dust mite (HDM) challenges vs. recorded in the natural environment were more accurate and precise predictors of asthma severity and control, lung function (FEV1), and mechanistic correlates of maladaptation. Correlates included elevated levels of peripheral blood CD4+ and CD8+ T-cells, eosinophils, and T-cell activation, as well as gene expression proxies for ineffectual epithelial injury/repair responses. Evoked symptom severity after HDM challenge appeared to be more closely related to levels of CD4+ and CD8+ T-cells than eosinophils, neutrophils, or HDM-specific IgE. CONCLUSIONS: Provocation studies support the concept that resilience, adaptation, and maladaptation to environmental disease triggers calibrate AA/ARC severity. Despite the ubiquity of aeroallergens, in response to these disease triggers in controlled settings (ie, ACC), most atopic persons manifest the resilient or adaptive phenotype. Thus, ARC/AA disease progression may reflect the failure to preserve the resilient or adaptive phenotype. The triangulation of CD8+ T-cell activation, airway epithelial injury/repair processes and maladaptation in mediating AA disease severity needs more investigation.

Pollen exposure is associated with risk of respiratory symptoms during the first year of life.

BACKGROUND: Pollen exposure is associated with respiratory symptoms in children and adults. However, the association of pollen exposure with respiratory symptoms during infancy, a particularly vulnerable period, remains unclear. We examined whether pollen exposure is associated with respiratory symptoms in infants and whether maternal atopy, infant's sex or air pollution modifies this association. METHODS: We investigated 14,874 observations from 401 healthy infants of a prospective birth cohort. The association between pollen exposure and respiratory symptoms, assessed in weekly telephone interviews, was evaluated using generalized additive mixed models (GAMMs). Effect modification by maternal atopy, infant's sex, and air pollution (NO2 , PM2.5 ) was assessed with interaction terms. RESULTS: Per infant, 37 ± 2 (mean ± SD) respiratory symptom scores were assessed during the analysis period (January through September). Pollen exposure was associated with increased respiratory symptoms during the daytime (RR [95% CI] per 10% pollen/m3 : combined 1.006 [1.002, 1.009]; tree 1.005 [1.002, 1.008]; grass 1.009 [1.000, 1.23]) and nighttime (combined 1.003 [0.999, 1.007]; tree 1.003 [0.999, 1.007]; grass 1.014 [1.004, 1.024]). While there was no effect modification by maternal atopy and infant's sex, a complex crossover interaction between combined pollen and PM2.5 was found (p-value 0.003). CONCLUSION: Even as early as during the first year of life, pollen exposure was associated with an increased risk of respiratory symptoms, independent of maternal atopy and infant's sex. Because infancy is a particularly vulnerable period for lung development, the identified adverse effect of pollen exposure may be relevant for the evolvement of chronic childhood asthma.

Fungal Spore Richness in School Classrooms is Related to Surrounding Forest in a Season-Dependent Manner.

Airborne fungal spores are important aeroallergens that are remarkably diverse in terms of taxonomic richness. Indoor fungal richness is dominated by outdoor fungi and is geographically patterned, but the influence of natural landscape is unclear. We aimed to elucidate the relationship between indoor fungal spore richness and natural landscape by examining the amount of surrounding forest cover. Passive sampling of airborne fungal spores was conducted in 24 schools in Taiwan during hot and cool seasons, and amplicon sequencing was used to study fungal spore (genus) richness targeting the internal transcribed spacer 2 (ITS2) region. In total, 693 fungal genera were identified, 12 of which were ubiquitous. Despite overall similarity of fungal spore richness between seasons, Basidiomycota and Ascomycota richness increased during the hot and cool seasons, respectively. Fungal spore richness in schools had a strong positive correlation with the amount of surrounding forest cover during the cool season, but not during the hot season. Fungal assemblages in schools were more similar during the hot season due to the increased ubiquity of Agaricomycetes genera. These observations indicate dispersal limitation at the kilometer scale during the cool season and increased long-distance dispersal during the hot season. Several allergenic fungi were commonly identified in schools, including some previously overlooked by conventional methods, which may be targeted as sensitizing agents in future investigations into atopic conditions. More generally, the relative importance of fungal spore richness in the development, chronicity, and severity of atopic conditions in children requires investigation.

Combination therapy of specific aeroallergens immunotherapy and omalizumab, in children with severe asthma.

BACKGROUND: In most cases, severe asthma in children has an allergic etiology, but allergen-specific immunotherapy (AIT) is contraindicated. OBJECTIVE: This study aimed at analyzing the safety and efficacy of AIT in patients with severe asthma treated with omalizumab (OM). METHODS: A descriptive real-life study was carried out by reviewing medical records. Effectiveness was measured by the degree of control (CAN questionnaire), number of hospitalizations per year, number of exacerbations per year, and maintenance treatment and lung function (FEV1). Some adverse reactions occurred (AAI-EAACI-WAO guidelines). RESULTS: The retrospective study included 29 patients up to 18 years of age with severe asthma with OM plus AIT treatment. AIT treatment was started in a cluster schedule when patients treated with OM achieved disease control. Before starting AIT, patients were treated with OM for 1 year for achieving asthmatic control. AIT to mites (51%), Alternaria (37.9%), or pollens (10.3%) was administered. After one year with OM plus AIT,statistically significant differences in CAN scores and FEV1 measures were observed (P < 0.001). No patients under treatment with OM plus AIT required hospital admission. During the clustering schedule, only 3/64 doses showed systemic adverse reactions. During the AIT maintenance treatment, 348 doses were administered, with no significant adverse reactions. CONCLUSION: In this population-based study in children with severe asthma, the combined treatment with OM plus AIT was safe and effective. This strategy allows these pediatric patients to be safely treated with AIT.

Spatiotemporal assessment of aeromycoflora under differing urban green space, sampling height, and meteorological regimes: the atmospheric fungiscape of Thessaloniki, Greece.

We studied the diversity and abundance of the airborne fungal spores in the city of Thessaloniki, Greece, for two consecutive years. Air samples were collected at one rooftop station (at 30 m) and six near-ground stations (at 1.5 m) that differed in the size and composition of adjacent green spaces. The effects of meteorological factors on airborne fungal spore concentrations were also explored. Cladosporium spores were dominant everywhere in the air of the city. The total concentration of the airborne fungal spores at 30 m was 10 times lower than near the ground. Differences in concentration and composition were far less pronounced among near-ground stations. The attributes of the fungal spore season did not change in a consistent way among stations and years. Concentrations at the near-ground stations matched the grouping of the latter into stations of high, intermediate, and low urban green space. Minimum air temperature was the primary meteorological factor affecting spore abundance, followed by relative humidity. Airborne fungal spores are more homogeneously distributed in the air of the city, but their concentrations decrease more rapidly with height than pollen.

Repetitive aeroallergen challenges elucidate maladaptive epithelial and inflammatory traits that underpin allergic airway diseases.

BACKGROUND: Signifying the 2-compartments/1-disease paradigm, allergic rhinoconjunctivitis (ARC) and asthma (AA) are prevalent, comorbid conditions triggered by environmental factors (eg, house dust mites [HDMs]). However, despite the ubiquity of triggers, progression to severe ARC/AA is infrequent, suggesting either resilience or adaptation. OBJECTIVE: We sought to determine whether ARC/AA severity relates to maladaptive responses to disease triggers. METHODS: Adults with HDM-associated ARC were challenged repetitively with HDMs in an aeroallergen challenge chamber. Mechanistic traits associated with disease severity were identified. RESULTS: HDM challenges evoked maladaptive (persistently higher ARC symptoms), adaptive (progressive symptom reduction), and resilient (resistance to symptom induction) phenotypes. Symptom severity in the natural environment was an imprecise correlate of the phenotypes. Nasal airway traits, defined by low inflammation-effectual epithelial integrity, moderate inflammation-effectual epithelial integrity, and higher inflammation-ineffectual epithelial integrity, were hallmarks of the resilient, adaptive, and maladaptive evoked phenotypes, respectively. Highlighting a crosstalk mechanism, peripheral blood inflammatory tone calibrated these traits: ineffectual epithelial integrity associated with CD8+ T cells, whereas airway inflammation associated with both CD8+ T cells and eosinophils. Hallmark peripheral blood maladaptive traits were increased natural killer and CD8+ T cells, lower CD4+ mucosal-associated invariant T cells, and deficiencies along the TLR-IRF-IFN antiviral pathway. Maladaptive traits tracking HDM-associated ARC also contributed to AA risk and severity models. CONCLUSIONS: Repetitive challenges with HDMs revealed that maladaptation to disease triggers may underpin ARC/AA disease severity. A combinatorial therapeutic approach may involve reversal of loss-of-beneficial-function traits (ineffectual epithelial integrity, TLR-IRF-IFN deficiencies), mitigation of gain-of-adverse-function traits (inflammation), and blocking of a detrimental crosstalk between the peripheral blood and airway compartments.

The association between outdoor allergens - pollen, fungal spore season and high asthma admission days in children and adolescents.

Periods when asthma admissions peaks have serious implications for asthma sufferers and hospitals. We assessed the association between aeroallergen exposure and childhood asthma peak periods during two grass pollen seasons using the Melbourne Air Pollen Children and Adolescent Health (MAPCAH) study conducted in Melbourne, Australia. Two peak periods were identified. Effect modifications by atopy and sex were considered. All pollen 2 days prior was associated with increased odds of these peak periods. Same day fungal spores, but not pollen, were important. Grass at lag 2 was associated with increased odds 1.03 (95%CI 1.01, 1.05) as was the same day Alternaria 1.02 (1.00, 1.04) per spore/m3 for boys. In addition to pollen, fungal spores particularly Alternaria may result in days of high exacerbations during pollen seasons. Further guidance is needed to better prepare families/carers with information about the increased risk of asthma attacks in children prior to pollen seasons.

Role of Secretoglobin+ (club cell) NFκB/RelA-TGFß signaling in aero-allergen-induced epithelial plasticity and subepithelial myofibroblast transdifferentiation.

Repetitive aeroallergen exposure is linked to sensitization and airway remodeling through incompletely understood mechanisms. In this study, we examine the dynamic mucosal response to cat dander extract (CDE), a ubiquitous aero-allergen linked to remodeling, sensitization and asthma. We find that daily exposure of CDE in naïve C57BL/6 mice activates innate neutrophilic inflammation followed by transition to a lymphocytic response associated with waves of mucosal transforming growth factor (TGF) isoform expression. In parallel, enhanced bronchiolar Smad3 expression and accumulation of phospho-SMAD3 was observed, indicating paracrine activation of canonical TGFßR signaling. CDE exposure similarly triggered epithelial cell plasticity, associated with expression of mesenchymal regulatory factors (Snai1 and Zeb1), reduction of epithelial markers (Cdh1) and activation of the NFκB/RelA transcriptional activator. To determine whether NFκB functionally mediates CDE-induced growth factor response, mice were stimulated with CDE in the absence or presence of a selective IKK inhibitor. IKK inhibition substantially reduced the level of CDE-induced TGFß1 expression, pSMAD3 accumulation, Snai1 and Zeb1 expression. Activation of epithelial plasticity was demonstrated by flow cytometry in whole lung homogenates, where CDE induces accumulation of SMA+Epcam+ population. Club cells are important sources of cytokine and growth factor production. To determine whether Club cell innate signaling through NFκB/RelA mediated CDE induced TGFß signaling, we depleted RelA in Secretoglobin (Scgb1a1)-expressing bronchiolar cells. Immunofluorescence-optical clearing light sheet microscopy showed a punctate distribution of Scgb1a1 progenitors throughout the small airway. We found that RelA depletion in Secretoglobin+ cells results in inhibition of the mucosal TGFß response, blockade of EMT and reduced subepithelial myofibroblast expansion. We conclude that the Secretoglobin-derived bronchiolar cell is central to coordinating the innate response required for mucosal TGFß1 response, EMT and myofibroblast expansion. These data have important mechanistic implications for how aero-allergens trigger mucosal injury response and remodeling in the small airway.