House Dust Mite Sensitization Research Articles

Trends of aeroallergen sensitization among children with respiratory allergy in Southern Thailand

Background: Respiratory allergy significantly impacts children’s health and quality of life, with inhaled allergens serving as prevalent triggers for respiratory symptoms. Aeroallergen sensitization, confirmed through the skin prick test (SPT), naturally evolves over time and is influenced by environmental factors specific to each region. Objective: This study aimed to review the updated 6-year trend of aeroallergen sensitization among children with asthma and allergic rhinitis in Southern Thailand. Methods: This retrospective study involved a review of patients aged ≤15 years diagnosed with asthma and/or allergic rhinitis, who underwent the SPT using 12 standardized aeroallergens. Results: The medical records of 1,393 children were reviewed, with 63% being male, and the mean age was 7.4 ± 3.3 years. Among them, 55.5% presented with allergic rhinitis alone, followed by 31.6% with asthma and allergic rhinitis, and 12.9% with asthma alone. Over the 6-year period, house dust mites emerged as the most common sensitized allergen, followed closely by cockroaches, maintaining a consistent trend of sensitization. Dermatophagoides pteronyssinus ranked as the predominant sensitized allergen across all diagnoses (63% in asthma with allergic rhinitis, 52.7% in allergic rhinitis, and 43.5% in asthma). Children diagnosed with both asthma and allergic rhinitis exhibited a higher prevalence of sensitization to house dust mites, cockroaches, Johnson grass, acacia, Candida albicans, and cat pelts compared with those with asthma or allergic rhinitis alone. Additionally, the prevalence of house dust mite and cockroach sensitization was notably higher in older children (≥5 years old) with respiratory allergies. Conclusion: House dust mites and cockroaches emerge as the 2 most prevalent sensitized aeroallergens among children diagnosed with asthma and/or allergic rhinitis, exhibiting consistent trends of sensitization over the past 6 years. The persistence of these causative allergens underscores the importance of meticulous environmental control measures for children affected by respiratory allergies.

Sublingual allergen immunotherapy prevents house dust mite inhalant type 2 immunity through dendritic cell-mediated induction of Foxp3+ regulatory T cells

Sublingual allergen immunotherapy (SLIT) is an emerging treatment option for allergic asthma, and a potential disease modifying strategy for asthma prevention. The key cellular events leading to such long term tolerance remains to be fully elucidated. We administered prophylactic SLIT in a mouse model of house dust mite (HDM) driven allergic asthma. HDM extract was sublingually administered over 3 weeks followed by intratracheal sensitization and intranasal challenges with HDM. Prophylactic SLIT prevented allergic airway inflammation and hyperreactivity with a low lab-to-lab variation. The HDM specific Th2 (CD4 T helper) response was shifted by SLIT towards a regulatory and Th17 response in lung and mediastinal lymph node (MLN). By using Der p 1 specific CD4+ T cells (1-DER), we found that SLIT blocked 1-DER T cell recruitment to the MLN and dampened IL-4 secretion following intratracheal HDM sensitization. Sublingually administered Der p 1 protein activated 1-DER T cells in the cervical lymph node (CLN) via CCR7+ migratory dendritic cells (DC). DCs migrating from the oral submucosa to the CLN after SLIT induced Foxp3+ regulatory T cells. When mice were sensitized with HDM, prior prophylactic SLIT increased Der p 1 specific Tregs and lowered Th2 recruitment in the lung. By using Foxp3-DTR mice, Tregs were found to contribute to the immunoregulatory prophylactic effect of SLIT on type 2 immunity. These findings in a mouse model suggest that DC-mediated functional Treg induction in oral mucosa draining LNs is one of the driving mechanisms behind the disease modifying effect of prophylactic SLIT.

MiR-4454 in Combined Allergic Rhinitis and Asthma Syndrome (CARAS): Clinical significance and mechanistic insights into airway inflammation.

Abnormal expression of non-coding microRNA is associated with the development of combined allergic rhinitis and asthma syndrome (CARAS). However, the function of miR-4454 in CARAS is unknown. Our study aimed to reveal the clinical significance and related mechanism of miR-4454 in CARAS. Blood samples from 38 cases of CARAS and 43 cases of healthy subjects were collected to detect the expression of miR-4454. House dust mite (HDM) sensitization and challenge-induced bronchial epithelial cells to simulate the asthma state model in vitro, miR-4454 mimics and inhibitor transfection to detect the expression level of pro-inflammatory cytokines, cell survival rate and migration ability, flow cytometry and western blot (WB) Detection of cell cycle, apoptosis and inflammation-related protein levels. Compared with healthy controls, the expression of miR-4454 in the blood of CARAS patients was significantly up-regulated, and IL-6 and IL-8 were significantly up-regulated in the HDM treatment group, indicating that the model induction was successful. After overexpression of miR-4454, cell proliferation and migration in the HDM-treated group were significantly inhibited, and the levels of early apoptosis and inflammation-related proteins (IL-17, IL-17RD, TNF-α, GCSF and NF-κB) were increased High; after inhibiting miR-4454, cell proliferation and migration were significantly enhanced, and the levels of apoptosis and inflammation-related proteins were decreased. This study found that inhibiting the expression of miR-4454 can improve HDM-induced cell injury, which may be related to miR-4454 regulating the activation of IL-17/NF-кB inflammatory axis.

Pitfalls in the diagnosis of house dust mite allergy

House dust mite (HDM) is the most significant indoor allergen, responsible for not only many cases of rhinoconjunctivitis but also for many cases of bronchial asthma, rendering it of considerable socioeconomic relevance. Besides symptomatic treatment and avoidance measures, allergen immunotherapy (AIT) is crucial, as the only causal, disease-modifying therapeutic approach. However, high diagnostic certainty is essential for initiating AIT. The challenge in making acorrect diagnosis lies in interpreting the demonstrated HDM sensitization regarding its clinical relevance (clinically silent sensitization vs. allergy). While the risk of allergy increases with the level of IgE titers against HDM extract, Der p1, or Der p2, as well as with the breadth of the molecular sensitization profile against HDM components (Der p1, Der p2, Der p23), no threshold can be defined for the presence of allergy, nor can sensitization to aspecific component be confidently considered allergy inducing. It should be noted that at least in Southern Bavaria, the prevalence of Der p23 sensitization is too low to be considered amajor allergen, and Der p23 is not able to molecularly differentiate all HDM sensitizations when added to the two major allergens Der p1 and Der p2. Evidently, HDM possesses adiverse profile of allergens, with some relevant ones possibly yet to be described. Unfortunately, patient history does not provide asufficient assessment of the clinical relevance of ademonstrated HDM sensitization, necessitating allergen provocation testing before initiating AIT with HDM, despite the relatively large effort involved.

Accurate determination of house dust mite sensitization in asthma and allergic rhinitis through cytometric detection of Der p 1 and Der p 2 binding on basophils (CytoBas)

House dust mite (HDM) is the most common allergen trigger globally for allergic rhinitis and atopic asthma. To expedite accurate confirmation of allergen sensitization, we designed fluorescent allergen tetramers to directly stain specific IgE on basophils to detect specific allergen sensitization using the flow cytometric CytoBas assay. Recombinant proteins of major HDM allergens (component), Der f 1, Der p 1, and Der p 2 were biotinylated and conjugated with fluorochrome streptavidins as tetramers. Blood samples from 64 patients who are HDM-allergic and 26 controls that are non-HDM-sensitized were incubated with allergen tetramers for evaluation of basophil binding (CytoBas) and activation (BAT) with flow cytometry. The tetramers effectively bound and activated basophils from patients who are allergic but not from controls who are nonsensitized. CytoBas with Der p 1 as a single allergen had comparable sensitivity and specificity (92% and 100%) to BAT (91% and 100%) in detecting allergen sensitization, as did CytoBas with Der p 2 (95% and 96%) to BAT (95% and 87%). Apositive staining for Der p 1 and/or Der p 2 in CytoBas was 100% sensitive and 96% specific for HDM allergy. CytoBas has diagnostic accuracy for group 1 and group 2 HDM allergens that is comparable to BAT, but with additional advantages of multiple allergen components in a single tube and no requirement for invitro basophil activation. These findings endorse a single, multiplex CytoBas assay for accurate and component-resolved diagnosis of aeroallergen sensitization in patients with allergic asthma and/or rhinitis.

Factors contributing to the diagnosis and onset prediction of perennial allergic rhinitis in high-risk children: A sub-analysis of the CHIBA study

BackgroundThis study aimed to clarify the diagnostic and predictive factors for perennial allergic rhinitis (PAR) onset in children by analyzing the results of the Chiba High-risk Birth Cohort for Allergy study, which examined newborns with a family history of allergies. MethodsOverall, 306 pregnant women were recruited. Their newborns were examined by otolaryngologists and pediatric allergists at 1, 2, and 5 years of age. Participants with clinical and laboratory data available at all consultation points were considered eligible. ResultsAmong 187 eligible participants, the prevalence rates of PAR were 2.1%, 4.3%, and 24.1% at 1, 2, and 5 years of age, respectively. AR-specific nasal local findings and eosinophils in nasal smear were observed in a substantial number of patients with PAR at 1 and 2 years of age. Factors present up to 2 years of age that were associated with PAR onset at 5 years of age, in descending order, were as follows: sensitization to house dust mites (HDM), nasal eosinophilia, and sensitization to cat dander. In 44 cases with HDM sensitization, nasal eosinophilia up to 2 years of age achieved a sensitivity of 76.0% and a specificity of 73.7% for predicting PAR onset at 5 years. ConclusionsRhinitis findings and nasal eosinophilia are useful auxiliary diagnostic items for pediatric PAR. Sensitization to HDM and nasal eosinophilia were the most influential factors associated with future PAR onset. A combination of these factors may facilitate the prediction of PAR onset.

Comparison of the General Characteristics of Patients with Severe Asthma Who Switched from Omalizumab to Mepolizumab versus Patients Who Responded to Omalizumab Treatment: A Real-Life Study

Introduction: Severe asthma is characterized by frequent recurrent airway symptoms and exacerbations, and these affect the quality of life. Biological agents can be used in the treatment of patients with severe asthma if the disease cannot be controlled with standard controller treatment. The aim of this study was to compare the clinical characteristics and laboratory data of patients with severe asthma who were switched from omalizumab to mepolizumab and patients with severe asthma who responded to omalizumab. Methods: The clinical characteristics and laboratory data of patients with severe asthma who responded to omalizumab and switched from omalizumab to mepolizumab were compared retrospectively. Results: Evaluation was made of a total of 79 patients, including 64 omalizumab responders and 15 who switched to mepolizumab from omalizumab. After omalizumab and mepolizumab treatment, the annual number of asthma attacks, the use of oral corticosteroid (OCS), the annual number of hospitalizations, and the eosinophil count significantly decreased (omalizumab: p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively; mepolizumab: p = 0.001, p = 0.001, p = 0.002, p = 0.001, respectively). After omalizumab treatment, the increase in forced expiratory volume in 1 s (FEV1) (%) and asthma control test (ACT) score were determined to be statistically significant (p < 0.001, p < 0.001, respectively). After mepolizumab treatment, the increase in ACT score was significant (p = 0.003). Drug allergy, chronic sinusitis with nasal polyps (CRSwNP), regular use of OCS, and high baseline eosinophil count (cells/µL) were associated with poor response to omalizumab treatment (odds ratio [OR] = 7.86, p = 0.003; OR = 52.92, p < 0.001; OR = 10.16, p = 0.004; OR = 0.99, p = 0.004, respectively). House dust mite sensitivity and high baseline FEV1 (%) were associated with good response to omalizumab treatment (OR = 0.29, p = 0.041; OR = 1.06, p = 0.03, respectively). The blood eosinophil count had diagnostic value in predicting the nonresponsiveness to omalizumab treatment (area under the curve [AUC]: 0.967, p < 0.001, cut-off: 510). Conclusion: A high pretreatment eosinophil count, concomitant CRSwNP, a history of drug allergy, and regular OCS use may be associated with poor response to omalizumab treatment in patients with severe asthma. Depending on the treatment response, treatment switching can be applied between biological agents. The results of the current study should be supported by multicenter studies.

Grandmaternal allergen sensitization reprograms epigenetic and airway responses to allergen in second-generation offspring.

Asthma susceptibility is influenced by environmental, genetic, and epigenetic factors. DNA methylation is one form of epigenetic modification that regulates gene expression and is both inherited and modified by environmental exposures throughout life. Prenatal development is a particularly vulnerable time period during which exposure to maternal asthma increases asthma risk in offspring. How maternal asthma affects DNA methylation in offspring and what the consequences of differential methylation are in subsequent generations are not fully known. In this study, we tested the effects of grandmaternal house dust mite (HDM) allergen sensitization during pregnancy on airway physiology and inflammation in HDM-sensitized and challenged second-generation mice. We also tested the effects of grandmaternal HDM sensitization on tissue-specific DNA methylation in allergen-naïve and -sensitized second-generation mice. Descendants of both allergen- and vehicle-exposed grandmaternal founders exhibited airway hyperreactivity after HDM sensitization. However, grandmaternal allergen sensitization significantly potentiated airway hyperreactivity and altered the epigenomic trajectory in second-generation offspring after HDM sensitization compared with HDM-sensitized offspring from vehicle-exposed founders. As a result, biological processes and signaling pathways associated with epigenetic modifications were distinct between lineages. A targeted analysis of pathway-associated gene expression found that Smad3 was significantly dysregulated as a result of grandmaternal allergen sensitization. These data show that grandmaternal allergen exposure during pregnancy establishes a unique epigenetic trajectory that reprograms allergen responses in second-generation offspring and may contribute to asthma risk.NEW & NOTEWORTHY Asthma susceptibility is influenced by environmental, genetic, and epigenetic factors. This study shows that maternal allergen exposure during pregnancy promotes unique epigenetic trajectories in second-generation offspring at baseline and in response to allergen sensitization, which is associated with the potentiation of airway hyperreactivity. These effects are one mechanism by which maternal asthma may influence the inheritance of asthma risk.

Inhibition of IL-17 ameliorates keratinocyte-borne cytokine responses in an in vitro model for house-dust-mite triggered atopic dermatitis

A subgroup of patients suffering from atopic dermatitis (AD) does not respond to biologics therapy targeting the key players of type-2 inflammation, and it is an ongoing discussion whether skin-infiltrating Th17 cells may underlie this phenomenon. This study aimed to investigate the potential of allergen-induced, immune-cell derived IL-17 on the induction of inflammatory processes in keratinocytes. Peripheral blood mononuclear cells derived from respectively sensitized AD patients were stimulated with house dust mite (HDM) extract and cell culture supernatants were applied subsequently in absence or presence of secukinumab to primary human keratinocytes. Hereby we confirm that the immune response of sensitized AD patients to HDM contains aside from type-2 cytokines significant amounts of IL-17. Blocking IL-17 efficiently reduced the stimulation-induced changes in keratinocyte gene expression. IL-17-dependent transcriptional changes included increased expression of the cytokines IL-20 and IL-24 as well as Suppressor of Cytokine Siganling 3 (SOCS3), a negative feedback-regulator of the STAT3/IL-17/IL-24 immune response. We conclude that the immune response to HDM can induce pro-inflammatory cytokines from keratinocytes in AD, which in part is mediated via IL-17. Targeting IL-17 may turn out to be a reasonable alternative therapy in a subgroup of patients with moderate to severe AD and HDM sensitization.

Difficult-to-treat asthma patients from ethnic minority groups in central England are at an enhanced risk of house dust mite sensitisation.

House dust mite (HDM) is the most common sensitising allergen in asthma. Ethnic minority groups (EMGs) in the UK are more likely to live in deprived conditionings with a greater exposure to HDM and other aero-allergens. To compare the ethnicity-based patterns of sensitisation to aero-allergens and the impact of ethnicity on clinical outcomes in patients with difficult-to-treat asthma (DTA). Data of patients with DTA were extracted from the registry of the Birmingham Regional Severe Asthma Service (BRSAS), which have a catchment population of 7.3million from Central England. Patients from White and EMG backgrounds were compared in terms of the prevalence of atopy, total serum immunoglobulin E (IgE), specific serum IgE (ssIgE) and asthma related clinical outcomes. Logistic regression analysis was conducted to explore ethnicity-based risk factors for HDM sensitisation. A total of 1272 patients [White 1016 (79.9%), EMG 256 (20.1%) EMG] with a median age of 51years (range 16-97) were included in the analysis. Patients from EMG were more likely (64%) to reside in the worst scale of index of multiple deprivation (IMD) than the White patients (25.5%), p<0.0001. Positive HDM sensitisation was more prevalent in the EMG than in the White group [142/216 (66%) versus 375/842 (45%), p<0.0001]. The median HDM ssIgE level was higher in the EMG than in the White group [3.0 KUA/L (IQR 0.06, 11.5) versus 0.1 (0.01, 3.0), p<0.000001]. The odds ratio for positive sensitisation to HDM conveyed by the EMG status was 2.61 (95%CI, 1.8-3.8), p<0.0001. Compared to the White group, the EMG had higher median total serum IgE [326 KU/L (115, 971) versus 114 (29.8, 434.8), p<0.000001], higher blood eosinophil count (0.36×109 (0.18, 0.62) versus 0.23 (0.1,0.47), p<0.000001), were marginally more atopic (79.2% vs. 75.6%, p=0.098) and were less likely to being on maintenance oral corticosteroids (22% vs. 39.7%, p<0.0001). In this DTA cohort, positive HDM sensitisation was greater amongst the EMG than the White patients. The EMG status was a significant risk factor for HDM sensitisation.

Tropical high altitude and severe asthma in adults: house dust mite sensitization and phenotypic distribution

Background There is a lack of information on house dust mite (HDM) sensitization and phenotype distribution in patients with severe asthma (SA) living permanently at high-altitude (HA) in tropical regions, which may be different. Objective The aim of this study was to characterize adults with SA in a tropical high altitude city (2,640 m): Bogotá, Colombia. Material and Methods This observational cross-sectional study included severe asthmatic outpatients (n = 129) referred to the ASMAIRE program of the Fundación Neumológica Colombiana in Bogotá (2,640 m). Clinical history, spirometry, total IgE, blood eosinophils, and skin prick test (SPT), including HDM allergens, were performed. Phenotype definitions: Allergic/atopic (AA): IgE ≥100 IU/mL and/or at least one positive SPT; eosinophilic (EOS): blood eosinophils ≥300 cells/µL; type 2-high: AA and/or EOS phenotype; type 2-low: non-AA/non-EOS phenotype (IgE <100 IU/mL, negative SPT, and blood eosinophils <300 cells/µL). Results A total of 129 adults with SA were included, 79.8% female. Phenotype distribution: AA: 61.2%; EOS: 37.2%; type 2-high: 72.1%; type 2-low: 27.9%. Among AA patients, HDM sensitization was present in 87% and 34.9% were non-eosinophilic. There was a significant overlap between the phenotypes. Conclusions In contrast to non-tropical high-altitude regions, we found a high frequency of HDM sensitization in patients with AA phenotype living in a tropical high-altitude city. We also found a discrete lower frequency of EOS phenotype with no other significant differences in the phenotypic distribution compared to that described at low altitudes. We propose that tropical location may modify the effect of high altitude on HDM concentrations and allergenicity.

Frequent Allergic Sensitization to Farmed Edible Insects in Exposed Employees

Exposure to insects used in pet food, scientific research, or live fish bait can cause an occupational allergy. The recent shift toward enhanced insect production for human consumption and animal feed will likely expose more employees. To investigate sensitization and symptoms in employees exposed to edible insects in Flanders. Fifteen insect-exposed employees were recruited and sensitization was explored by skin prick test, basophil activation test, and immunoblotting. Lung function, FeNO, histamine provocation, and sputum induction were studied. Airborne dust sampling was performed and proteins were studied by silver stain and immunoblotting. Sixty percent of employees self-reported upper respiratory tract symptoms related to insect exposure. Ten employees (71.4%) had a positive histamine provocation test concentration causing a 20% drop in FEV1 less than 8 mg/mL and four (26.7%) had FeNO levels above 25 ppb. Four employees (30.7%) had a positive skin prick test for at least one insect, and seven (58.3%) had a positive basophil activation test. In eight participants with insect sensitization, four (50%) had co-occurring house dust mite sensitization. Two participants had strong IgE binding to a 50-kDa migratory locust allergen, one to a 25-kDa mealworm allergen, and one to mealworm α-amylase. In one center, facility adjustment resulted in a substantial decrease in the inhalable dust fraction. Insect exposure leads to high levels of sensitization among employees. Most employees reported symptoms of the upper respiratory system, and two-thirds of employees had bronchial hyperreactivity. Prevention and health surveillance will be important in the developing insect-rearing industry.

Severe Anaphylactic Reactions to Home Doses of Oral Immunotherapy for Food Allergy.

Severe anaphylactic reactions to home-doses may occur during food allergy oral immunotherapy (OIT). To study the rate and risk factors for such reactions. All patients aged >3.5 years who completed OIT in a single center, between April-2010 and January-2020, were studied. All home epinephrine-treated reactions (HETRs) were identified. High-grade HETRs (HG-HETRs) were defined as HETR involving respiratory (SpO2 ≤94%), cardiovascular (low blood pressure), or CNS (loss of consciousness) impairment. The rate and risk factors for HG-HETRs were investigated. A total of 1637 OIT treatments were studied: milk, 880; peanut, 346; tree-nuts, 221; sesame, 115; and egg, 75. Of 390 identified HETRs, 30 HG-HETRs occurred during 27 treatments (1.65% of all treatments). Nearly all (26/30) were during milk OIT in patients with HDM-sensitization and asthma (26/30 each). Of the 30 HG-HETRs, 21 recovered with 1-2 epinephrine treatments, but 9 cases (0.55% of all treatments) did not respond to a second dose of epinephrine and were deemed refractory anaphylaxis. Three patients required ICU admission, and 3 received epinephrine drip but none required ventilatory support. Risk factors for HG-HETRs included milk-OIT (p=0.031), asthma (p=0.02) and house dust mite (HDM) sensitization (p=0.02). No specific triggers for HG-HETR were identified. Of patients with HG-HETRs, 25.9% were fully desensitized, including the 4 non-milk treated patients, 22.2% were partially desensitized and 51.9% failed. HG-HETRs and particularly refractory anaphylactic reactions to home OIT doses are uncommon. While milk OIT, asthma and HDM sensitization are the main risk factors for such reactions, identification of patients at risk is challenging.

Patterns of aeroallergen sensitization in asthma patients identified by latent class analysis: A cross-sectional study in China.

This cross-sectional study aimed to identify latent sensitization profiles of asthma patients in mainland China, unveiling the association between regional differences and sensitization patterns. 1056 asthma participants from 10 medical centers divided into eastern and western cohorts were clustered into four individual sensitization patterns, respectively, by using an unsupervised statistical modeling method, latent class analysis (LCA), based on the levels of 12 aeroallergens specific IgE reactivities. Moreover, differences in clinical characteristics and environmental exposures were compared in different sensitization patterns. Four distinct sensitization patterns in the two cohorts were defined as follows, respectively. Eastern cohort: Class 1: "High weed pollen and house dust mites (HDMs) sensitization" (8.87%), Class 2: "HDMs dominated sensitization" (38.38%), Class 3: "High HDMs and animal dander sensitization" (6.95%), Class 4: "Low/no aeroallergen sensitization" (45.80%). Western cohort: Class 1: "High weed pollen sensitization" (26.14%), Class 2: "High multi-pollen sensitization" (15.02%), Class 3: "HDMs-dominated sensitization" (10.33%), Class 4: "Low/no aeroallergen sensitization" (48.51%). Of note, the significant statistical difference in age, asthma control test score (ACT) and comorbidities were observed within or between different sensitization patterns. Exposure factors in different sensitization patterns were pointed out. Asthmatic patients with distinct sensitization patterns were clustered and identified through the LCA method, disclosing the relationship between sensitization profiles of multiple aeroallergens and geographical differences, providing novel insights and potential strategies for atopic disease monitoring, management and prevention in clinical practice.

Retinoic Acid-Related Orphan Receptor α Is Required for Generation of Th2 Cells in Type 2 Pulmonary Inflammation.

The transcription factor retinoic acid-related orphan receptor α (RORα) is important in regulating several physiological functions, such as cellular development, circadian rhythm, metabolism, and immunity. In two invivo animal models of type 2 lung inflammation, Nippostrongylus brasiliensis infection and house dust mite (HDM) sensitization, we show a role for Rora in Th2 cellular development during pulmonary inflammation. N. brasiliensis infection and HDM challenge induced an increase in frequency of Rora-expressing GATA3+CD4 T cells in the lung. Using staggerer mice, which have a ubiquitous deletion of functional RORα, we generated bone marrow chimera mice, and we observed a delayed worm expulsion and reduced frequency in the expansion of Th2 cells and innate lymphoid type 2 cells (ILC2s) in the lungs after N. brasiliensis infection. ILC2-deficient mouse (Rorafl/flIl7raCre) also had delayed worm expulsion with associated reduced frequency of Th2 cells and ILC2s in the lungs after N. brasiliensis infection. To further define the role for Rora-expressing Th2 cells, we used a CD4-specific Rora-deficient mouse (Rorafl/flCD4Cre), with significantly reduced frequency of lung Th2 cells, but not ILC2, after N. brasiliensis infection and HDM challenge. Interestingly, despite the reduction in pulmonary Th2 cells in Rorafl/flCD4Cre mice, this did not impact the expulsion of N. brasiliensis after primary and secondary infection, or the generation of lung inflammation after HDM challenge. This study demonstrates a role for RORα in Th2 cellular development during pulmonary inflammation that could be relevant to the range of inflammatory diseases in which RORα is implicated.

Early inhalant allergen sensitization at component level: an analysis in atopic Dutch children.

Allergic rhinitis is a common respiratory disease in children and sensitization to inhalant allergens plays a significant role in its development. However, limited knowledge exists regarding sensitization profiles of inhalant allergen components in atopic children, particularly in the very young individuals. Understanding these profiles could provide insights into the early development of allergic rhinitis. The objective of this cross-sectional retrospective study was to evaluate the IgE-sensitization profiles to multiple inhalant allergen components and their clinical relevance in Dutch atopic children, with specific focus on children under the age of 4 years. A total of 243 atopic children were included in the study and sensitization profiles were analyzed using multiplex microarray analysis (ISAC). Clinical information was obtained from records of a pediatric allergy outpatient clinic between 2011 and 2020. Specific IgE responses to inhalation allergen components from five allergen sources (grass pollen, tree pollen, house dust mite, cat and dog), were examined. The study encompassed children of different age groups and compared those with and without symptoms. The results demonstrated that sensitization to inhalant allergen components was present in 92% of the cohort. Sensitization was already evident at a young age (87%), including infancy, with a rapid increase in prevalence after 1 year of age. House dust mite emerged as the most predominant sensitizing allergen in early childhood, followed by tree pollen in later years. Sensitization patterns were similar between symptomatic and asymptomatic children, although symptomatic children exhibited higher frequencies and values. The sensitization profiles in very young children were comparable to those of children across all age groups. These findings highlight the presence of sensitization to inhalant allergen components and the early onset of allergic rhinitis before the age of 4, including infancy, in Dutch atopic children. Notable allergen molecules in Dutch atopic children under the age of 4 years include Bet v 1, Fel d 1, Der f 1, Der p 1, Der p 10 and Phl p 4, with house dust mite sensitization being the most common among Dutch infants. Moreover, the prevalence of sensitization to inhalant allergens in this Dutch cohort surpassed that of general European populations, emphasizing the importance of early assessment and management of allergic rhinitis in young atopic children.

Role of Caspase-11 in house dust mites-mediated lung inflammation

Abstract Asthma is a long-term recurring inflammatory lung disorder characterized by mucus hypersecretion, cellular infiltration, chronic airway inflammation and bronchial hyper-responsiveness. House dust mites (HDM), such as Dermatophagoides pteronyssinus, are an unsurpassed cause of atopic sensitization and the major causes of allergic asthma worldwide. The multiprotein complexness of the canonical and noncanonical inflammasomes assemble in response to pathogen or danger-associated molecular patterns (PAMPs or DAMPs). We have shown that caspase-11 expression is induced in vitro in response to HDM. Treatment with TH2 cytokines such as IL-4 and IL-13 mediates caspase-11 expression. Additionally, caspase-11−/−macrophages show reduced release of IL-6, IL-12, and KC, and express lower levels of costimulatory molecules (e.g., CD40, CD86 and MHCII) in response to HDM stimulation. Notably, similar level of IgE responses and similar degree of hypothermia in response to nasal HDM challenge were seen in WT and caspase-11−/−mice following HDM sensitization. However, altered inflammatory responses and reduced neutrophilia in bronchiolar alveolar lavage fluid (BALF) and in representative histopathological lung tissues were seen in the caspase-11−/−mice. Therefore, caspase-11 is a regulator of airway inflammation in response to HDM exposure.

Comparison of Loratadine and Ketotifen Pharmacotherapy in Cases of Chronic Cough in Children: A Study at Petrokimia Gresik Hospital, Indonesia

Objectives: To compare the efficacy of loratadine and ketotifen pharmacotherapy in cases of chronic cough in children at Petrokimia Gresik Hospital, Indonesia.&#x0D; Materials and Methods: A retrospective case-control study on 127 chronic cough children aged less than 6 years old was done. All subjects went through a period of restrictive diet for 2-4 weeks. If the symptoms relieved, subjects were reintroduced previous daily diet gradually. All subjects were randomized to take loratadine powder (54%), once daily or ketotifen powder (46%), twice daily for 2-4 weeks, for chronic cough pharmacotherapy. Cough symptoms was evaluated during next visit. At those visits, the adverse event was also evaluated.&#x0D; Results: Of the 187 subjects enrolled, 60 dropped out. Thus, 69 children remained on loratadine, and 58 on ketotifen. Of all research subjects, only 10% experienced improvement (P= 0.582). In the non-improved group, 35% of the subjects also suffered from acute maxillary sinusitis. There were no adverse events in all groups.&#x0D; Conclusion: There were no significant difference between loratadine and ketotifen pharmacotherapy in cases of chronic cough in children at Petrokimia Gresik Hospital, Indonesia. Further investigation to look after other common uncontrolled triggers such as house dust mite sensitization, need to be done in this study, so that comprehensive therapy can be given.

Analysis of intronic SNP (rs4147358) and expression of SMAD3 gene in Atopic Dermatitis: A case-control study

BackgroundAtopic Dermatitis (AD) is a multifactorial cutaneous disorder associated with chronic inflammation of the skin. Growing evidence points to TGF-β/SMAD signaling as a key player in mediating inflammation and the subsequent tissue remodeling, often resulting in fibrosis. This study investigates the role of a core transcription factor involved in TGF-β signaling i.e., SMAD3 genetic variants (rs4147358) in AD predisposition and its association with SMAD3 mRNA expression, serum IgE levels, and sensitization to various allergens in AD patients. MethodsA total of 246 subjects including 134 AD cases and 112 matched healthy controls were genotyped for SMAD3 intronic SNP by PCR-RFLP. mRNA expression of SMAD3 was determined by quantitative Real-Time PCR (qRT-PCR), Vitamin-D levels by chemiluminescence, and total serum IgE levels by ELISA. In-vivo allergy testing was performed for the evaluation of allergic reactions to house dust mites (HDM) and food allergens. ResultsA significantly higher frequency of mutant genotype AA (cases: 19.4% vs controls: 8.9%) (OR = 2.8, CI = 1.2 – 6.7, p = 0.01) was observed in AD cases. The mutant allele ‘A’ also showed a 1.9-fold higher risk for AD compared to the wild allele ‘C’ indicating that the carriers of the A allele have a higher risk for AD predisposition (OR-1.9, CI = 1.3–2.8, p < 0.001). In addition, quantitative analysis of SMAD3 mRNA in peripheral blood showed 2.8-fold increased expression in AD cases as compared to healthy controls. Stratification analysis revealed the association of the mutant AA genotype with deficient serum Vitamin D levels (p = 0.02) and SMAD3 mRNA overexpression with HDM sensitization (p = 0.03). Furthermore, no significant association of genotypes with SMAD3 mRNA expression was observed. ConclusionOur study indicates that SMAD3 intronic SNP bears a significant risk of AD development. Moreover, overexpression of SMAD3 mRNA and its association with HDM sensitization highlights the possible role of this gene in AD pathogenesis.

Nafamostat has anti-asthmatic effects associated with suppressed pro-inflammatory gene expression, eosinophil infiltration and airway hyperreactivity.

Asthma is characterized by an imbalance between proteases and their inhibitors. Hence, an attractive therapeutic option could be to interfere with asthma-associated proteases. Here we exploited this option by assessing the impact of nafamostat, a serine protease inhibitor known to neutralize mast cell tryptase. Nafamostat was administered in a mouse model for asthma based on sensitization by house dust mite (HDM) extract, followed by the assessment of effects on airway hyperreactivity, inflammatory parameters and gene expression. We show that nafamostat efficiently suppressed the airway hyperreactivity in HDM-sensitized mice. This was accompanied by reduced infiltration of eosinophils and lymphocytes to the airways, and by lower levels of pro-inflammatory compounds within the airway lumen. Further, nafamostat had a dampening impact on goblet cell hyperplasia and smooth muscle layer thickening in the lungs of HDM-sensitized animals. To obtain deeper insight into the underlying mechanisms, a transcriptomic analysis was conducted. This revealed, as expected, that the HDM sensitization caused an upregulated expression of numerous pro-inflammatory genes. Further, the transcriptomic analysis showed that nafamostat suppressed the levels of multiple pro-inflammatory genes, with a particular impact on genes related to asthma. Taken together, this study provides extensive insight into the ameliorating effect of nafamostat on experimental asthma, and our findings can thereby provide a basis for the further evaluation of nafamostat as a potential therapeutic agent in human asthma.