House Dust Mite Allergic Rhinitis Research Articles

Clinical benefits with 300 IR HDM SLIT tablet in Europeans with house dust mite allergic rhinitis: Post hoc analysis of a large phase 3 trial

BackgroundHouse dust mite (HDM)-induced allergic rhinitis (AR) is a major cause of allergic respiratory disease. The efficacy and safety of the 300 IR HDM sublingual immunotherapy (SLIT) tablet in patients with moderate-to-severe HDM-AR was confirmed in a large, international, phase 3 randomized controlled trials (RCTs). Here, we analyzed the results in the European population. MethodsData from 91 European centers that participated in the international, double-blind, RCT (EudraCT 2014-004223-46, NCT02443805) with the 300 IR HDM SLIT tablet versus placebo over 12 months were analyzed post hoc. The treatment effect in European adults and adolescents was notably assessed through the European Academy of Allergy and Clinical Immunology (EAACI)-recommended combined symptom and medication score (CSMS0-6, pre-defined endpoint) and the total combined rhinitis score (TCRS0-24, post hoc endpoint, also balanced) during the primary evaluation period (4 weeks at the end of treatment period) using analysis of covariance (ANCOVA). ResultsThere were 818 patients who comprised the modified full analysis set in Europe. Over the primary period, the differences in CSMS0-6 and TCRS0-24 between the 300 IR and placebo groups were statistically significant (p < 0.0001): −0.32 (95%CI [-0.46; −0.17]) and −1.28 (95%CI [-1.63; −0.94]), respectively, with relative differences of −20.9% and −21.2%. All post hoc and the rhinoconjunctivitis quality of life endpoints were significantly improved with 300 IR versus placebo. The 300 IR HDM tablet was generally well tolerated. ConclusionThis RCT sub-analysis confirmed the 300 IR HDM SLIT tablet is an effective and safe treatment for European adults and adolescents with HDM-AR with clinically meaningful benefits from the patients' perspective. Trial registrationNCT02443805. Registered on April 29, 2015./EudraCT 2014-004223-46. Registered on September 16, 2015.

SQ HDM sublingual immunotherapy tablet for the treatment of HDM allergic rhinitis and asthma improves subjective sleepiness and insomnia: an exploratory analysis of the real-life CARIOCA study.

There are still gaps in the knowledge regarding the effectiveness of house dust mite (HDM) sublingual immunotherapy (SLIT) on allergic rhinitis (AR) and asthma (AA)-associated sleep disorders. A non-interventional study was conducted to assess the effect of the Standardized quality (SQ) HDM SLIT-tablet on safety and symptoms in adults with HDM respiratory allergies. The aim was to describe the status of insomnia and daytime sleepiness in AR and/or AA patients treated with the SQ HDM SLIT-tablet. This was a 12-month multicenter, longitudinal and prospective study. Participants started the SQ HDM SLIT-tablet for moderate-to-severe HDM AR, persistent despite the use of symptom-relieving medication; or HDM AA not well controlled by inhaled corticosteroids and associated with mild-to-severe HDM AR. Sleep symptoms were measured using the Insomnia Severity Index (ISI) questionnaire and the Epworth Sleepiness Scale (ESS). A total of 1,526 adult patients were enrolled and 1,483 were included in the analysis. At baseline, 41.5% of patients reported sleep disorders: 77.0% of them had insomnia and 28.9% suffered from excessive daytime sleepiness. Insomnia was significantly more frequent among patients with uncontrolled AR (83.1%) than those with controlled AR (52.6%) (p<0.0001). Over time, 48.3% and 59.7% of patients reported an improvement greater than the minimal clinically important difference on the ISI and ESS scales respectively. In patients with HDM AR and/or asthma associated sleep disorders, an improvement in subjective insomnia and sleepiness was observed after one year of treatment with the SQ HDM SLIT-tablet in a real-life setting.

Sodium Chloride versus Lactose as a Carrier for House Dust Mite Allergen in Allergen Chamber Studies: A Clinical Study to Assess Noninferiority

Introduction: In the Fraunhofer allergen challenge chamber (ACC), a standardized, universal, good manufacturing practice-conforming technology using a spray dried solution of lactose (L) and allergen extract has been established. In this study, we investigated the noninferiority of hypertonic sodium chloride (S) versus L as a carrier for house dust mite (HDM) allergen to simplify manufacturing, reduce costs, and allow for wider use. Methods: Using a participant-blinded, sham exposure-controlled, single-arm, sequential intervention study, we challenged adults with HDM allergic rhinitis five times in the ACC. Participants were first exposed to S, L, and clean air (block 1), followed by S + HDM and L + HDM (block 2). Primary endpoints were mean total nasal symptom score (TNSS) and mean nasal secretion weight. Results: 19 participants were enrolled in the study (10 females; mean age 32 years [22–49], 4 with mild allergic asthma). The safety profile of S + HDM and L + HDM was similar; eight participants experienced mild procedure-related adverse events including tiredness, cough, and dyspnea. Due to dropouts, 13 participants completed the study and were evaluated. Mean TNSS and nasal secretion were as follows: S 0.98, 0.28 g; L 1.1, 0.20 g; clean air 1.1, 0.23 g; S + HDM 5.7, 4.8 g; L + HDM 5.1, 5.1 g. Separate block 1/block 2 MANOVAs with TNSS and nasal secretion as dependent variables revealed no significant differences between the carriers, neither alone and compared with clean air (p = 0.2059, Wilk’s λ = 0.78) nor combined with HDM (p = 0.3474, Wilk’s λ = 0.89). Noninferiority of S was established using a meta-analysis-based minimal clinical important difference of −0.55: mean TNSS difference between S + HDM and L + HDM was 0.62 (90% CI: −0.51 to 1.74). Conclusion: S as an HDM carrier was safe and well tolerated. It was noninferior to L which makes it an adequate and easy-to-use carrier substitute.

The relationship of D. pteronyssinus allergic component sIgE and sIgG4 in house dust mite allergic rhinitis or/and allergic asthma patients

Objective: House-dust mite sensitization is an important cause of allergic asthma and/or rhinitis in southern China. This study aimed to analyze the immune effect and relationship between the Dermatophagoides pteronyssinus components specific immunoglobulin E (sIgE) and sIgG₄. Methods: The serum levels of sIgE and sIgG₄ to D. pteronyssinus allergen components Der p 1, 2, 3, 5, 7, 10, and 23 were detected in 112 patients with allergic rhinitis (AR) and/or allergic asthma (AA). Results: Overall, Der p 1 had the highest positive rate of sIgE (72.3%), followed by Der p 2 (65.2%) and Der p 23 (46.4%). Meanwhile, the highest positive rates of sIgG₄ were for Der p 2 (47.3%), Der p 1 (33.0%), and Der p 23 (25.0%). The patients with AR and AA had a higher positive rate (43.4%) of sIgG₄ than that in the patients with AR (42.4%) and the patients with AA (20.4%; p = 0.043). In patients with AR, the positive rate of sIgE in Der p 1 (84.8%) was higher than that in sIgG₄ (42.4%; p = 0.037), but the positive rate of sIgG₄ in Der p 10 (21.2%) was higher than that in sIgE (18.2%; p < 0.001). Most of the patients were positive for sIgE and sIgG₄ of Der p 2 and Der p 10 at the same time. However, positive results for sIgE alone were just found in Der p 7 and Der p 21. Optimal scale analysis showed that Der p 2, Der p 7, and Der p 21 sIgG₄ were closely related to AR and AA (Cronbach α = 0.917). Conclusion: Herein, the D. pteronyssinus allergen components showed different characteristics among the patients with AR, patients with AA, and patients with AR and AA in southern China. Thus, sIgG₄ may be play an important role in allergic reactions.

Evaluation of the safety of dose escalation period of subcutaneous specific allergic immunotherapy in patients with rhino-conjunctivitis or allergic asthma previously vaccinated against SARS-CoV-2

BACKGROUND: More than 90% of the Spanish population has been vaccinated against the SARS-CoV-2 virus in our setting. The administration of this vaccine is not contraindicated in allergic subjects; however, it is unknown whether any precaution should be taken when initiating subcutaneous allergen immunotherapy after this vaccination. The objective of the study was to analyze the safety of subcutaneous allergen immunotherapy during the dose escalation phase in subjects sensitized to pollens or mites previously vaccinated against SARS-CoV-2. METHODS: An observational study with retrospective data collection from protocolled patients' medical records was designed. Outpatients older than 12 years with diagnosis of pollen or house dust mite allergic rhinitis with or without bronchial allergic asthma were selected who had completed the subcutaneous immunotherapy dose escalation phase. A complete SARS-CoV-2 vaccination was required for the inclusion. RESULTS: Three hundred and seventy-nine patients were included by 53 investigators. The mean age was 31 years old and 55,9% female. Time from last SARS-Cov-2 vaccination dose to subcutaneous immunotherapy initiation was 4.1 months (95%CI 3.8-4.4). subcutaneous immunotherapy with a pollen allergoid was administered to 135 patients (35.6%) with a total of 739 injections, while subcutaneous immunotherapy using a house dust mite allergoid was administered to 244 patients (64.4%) with a total of 1311 doses. During the dose escalation phase with the pollen allergoid, 45 patients (33.3%) suffered 93 local adverse reactions (12.6% of injections), while 17 patients (12.6%) experienced 17 systemic allergic reactions (2.3% of injections) of them 14 were World Allergy Organization Grade 1 and 3 of Grade 2. During the dose escalation phase with the house dust mite allergoid, 55 patients (22.5%) reported 133 local adverse reactions (10.1% of injections), and 7 patients (2.9%) showed 7 World Allergy Organization Grade 1 systemic reactions (0.5% of injections). No systemic reactions Grade 3 or higher were reported. CONCLUSIONS: The well-known safety profile of the subcutaneous allergen immunotherapy using pollen or house dust mite allergoids has not been changed after the SARS-CoV-2 vaccine administration. No relevant differences in the incidence of local or systemic allergic reactions during the dose escalation phase were identified, so it is considered that the patient’s safety has not been compromised to initiate this treatment after the SARS-CoV-2 vaccine administration.

The effect of the COVID-19 pandemic on long-term treatment compliance and disease control in children with persistent asthma.

No long-term data exists on asthma treatment compliances (ATC), exacerbations (AE), and control (AC) during the COVID-19 pandemic in children. This study aimed to evaluate ATC, AE, AC and the related factors among children with persistent asthma (PA) within the first year of the pandemic Methods. Children aged 6-18 years with PA who were under regular inhaled corticosteroid treatment for at least a year prior to the first COVID-19 case in Türkiye were included. Data on AE and AC were collected from medical files. Factors affecting ATC and AC as well as COVID-19 history were assessed by means of a questionnaire. The study included 247 cases. COVID-19 was detected in 14.5% of them. In the first year of the pandemic, ATC decreased to 56.7% and the most common reason was the absence of asthma symptoms. There was a significant improvement in AC (p < 0.001). The number of upper respiratory tract infections (URTI) and AE were significantly decreased during the first year of the pandemic (p < 0.001). COVID-19 infection, smoking in the household, school attendance, a family member working outside the home, house dust mite sensitization or allergic rhinitis had no significant effect on AC (p > 0.05). Regression analysis determined that children who did not have any URTI had 2.4 times better AC compared to those who had (p= 0.02; %95 CI: 1.1-5.4). Although ATC decreased significantly in the long-term in the first year of the pandemic, significant improvement was observed in AE and AC compared to the previous year, which was related only to not having URTI.

Exposure to House Dust Mite Allergen and Endotoxin in Early Life and Sensitization and Allergic Rhinitis: The JECS.

The association between endotoxin and allergic rhinitis (AR) is not conclusive. The aim of this study was to determine the association between endotoxin and house dust mite (HDM) allergens in dust, and HDM sensitization and AR among Japanese infants. This study included 4188 participants in the Sub-Cohort Study of the Japan Environment and Children's Study. Dust was collected from children's mattresses at age 18 months and endotoxin and HDM allergen levels were measured. A logistic regression model was used to analyze the association between endotoxin or HDM allergen and the sensitization to HDM (specific-IgE) at age 2 and AR at age 3. The median (interquartile range) endotoxin level was 375.1(186.9-826.5) EU/m2 and the Der 1 (Der p 1 + Der f 1) level was 51.2 (14.8-168.6) ng/m2. There were significant positive associations between endotoxin and HDM sensitization (Der f 1, adjusted odds ratio [aOR] quartile [Q] 4 vs. Q1, 1.44, 95% CI, 1.04-2.00; Der p 1, aOR Q4 vs. Q1, 1.56, 95% CI, 1.12-2.16). There were also significant positive associations between Der 1 exposure and HDM sensitization (Der f 1, aOR Q3 vs. Q1, 1.75, 95% CI, 1.26-2.44; aOR Q4 vs. Q1, 2.98, 95% CI, 2.15-4.13; Der p 1, aOR Q3 vs. Q1, 1.91, 95% CI, 1.37-2.66; aOR Q4 vs. Q1, 2.91, 95% CI, 2.09-4.05). There were, however, no associations between endotoxin or Der 1 and AR. In the population residing mostly in non-farming settings, both endotoxin and HDM allergens in dust were associated with an increased risk of HDM allergen sensitization, but not with AR.

Sensitisation profile of Chinese allergic rhinitis patients and effectiveness of ajoint allergy-ENT clinic.

PurposeHouse dust mite (HDM) is the predominant cause of allergic rhinitis (AR) in Hong Kong but remains under-diagnosed and -treated. The association between patient-reported outcome measures (PROMs) and nasoendoscopy findings for AR have also not been investigated. This study investigated the demographics, sensitisation patterns, quality of life, use of sublingual immunotherapy and the association of PROMs and nasoendoscopy findings in AR patients through the first allergist–otorhinolaryngologists AR joint (ARJ) clinic in Hong Kong.MethodsThis single-centred, retrospective observational study was conducted between January 2021 and December 2021. Clinical data from AR patients attending the ARJ clinic were analysed to identify the prevalence of HDM allergens, change in PROMs and the association of PROMs with nasoendoscopy scores.ResultsThe three most common sensitising HDM allergens were Dermatophagoides pterynosinus (94.4%), Dermatophagoides farinae (88.9%) and Euroglyphus maynei (88.9%). At the 13- to 32-week follow-up (median 28 weeks), patients who attended the ARJ clinic had significant improvement in Total Nasal Symptom Score (TNSS; p = 0.038). The visual analogue scale (VAS) was associated with nasoendoscopy score (p = 0.018). Patients using SLIT (sublingual immunotherapy) showed overall improvements in PROMs.ConclusionThe ARJ clinic significantly improved AR symptoms. SLIT was effective and safe for patients who failed conventional treatments. VAS positively correlated with nasoendoscopy findings. Testing for Dermatophagoides pterynosinus as a single agent during skin testing was sufficient for the diagnosis of HDM AR and should be prioritized when resources are restricted. Further studies should be done to investigate the treatment outcome of AR patients and the effectiveness of SLIT in the Chinese population.Supplementary InformationThe online version of this article (10.1007/s40629-022-00218-5) contains supplementary material, which is available to authorized users.

Metagenome-wide association of gut microbiome features in children with moderate-severe house dust mite allergic rhinitis

Objective:To draw a distinct gut microbiota pattern of children with moderate-severe dust mite-induced allergic rhinitis（DAR） and healthy children. Methods:3-10 years old moderate-severe DAR children（68 cases） and healthy children（38 cases） were involved in this study. General information was collected through questionnaires, and fecal samples were collected for metagenomic sequencing. MetaPhlAn3 was used to generate the microbiota composition abundance in detail, and Alpha and Beta diversity changes were calculated. The difference in species abundance at different taxonomic levels were compared. Differences in functional pathways were compared by LEfSe analysis. Results:The diversity of gut microbiota in children with moderate-severe DAR didn't change significantly compared with healthy children. A total of 37 microbial communities or species with significant abundance difference were found, mainly included Lachnoclostridium, Prevotella, Blautia wexlerae, Prevotella copri, Eubacterium eligens, Eubacterium sp CAG 180, etc. However, the metabolism functions of gut microbiota in children with moderate-severe DAR changed compared with healthy children. Various of fatty acids anabolism enhanced in DAR children. Conclusion:Compared with healthy children, there was no significant difference in gut microbial diversity in moderate-severe DAR children. The abundance of a series of specific microbe species had a marked alteration in DAR, accompanied with changes in certain microbial functional pathways.

Blocking function of allergen-specific immunoglobulin G, F(ab')2, and Fab antibodies prepared from patients undergoing Dermatophagoides pteronyssinus immunotherapy

BackgroundThe blocking function of allergen-specific F(ab')2 [sF(ab')2] and Fab (sFab) fragment antibodies prepared from allergen immunotherapy–induced specific immunoglobulin G (sIgG) has not been fully investigated. ObjectiveTo investigate the inhibitory function of sIgG, sF(ab')2, and sFab antibodies in patients undergoing Dermatophagoides pteronyssinus (Der-p) subcutaneous immunotherapy (SCIT). MethodsThis study involved 10 subjects (aged 18-42 years) with house dust mite allergic rhinitis or asthma who received a 156-week course of Der-p SCIT. Total IgG levels were purified from the serum of the participants at weeks 0 and 156 by protein A affinity chromatography. Der-p sIgG was purified by affinity chromatography with Der-p as a ligand at week 156. The sF(ab')2 and sFab antibodies were prepared from Der-p sIgG by treatment with pepsin and papain, respectively. Furthermore, IgE-facilitated allergen binding assay, basophil activation inhibition test, and cytokine release inhibition assay were used to assess the inhibitory function of Der-p sIgG, sF(ab')2, and sFab antibodies. ResultsWe found that the Der-p sIgG, sF(ab')2, and sFab antibodies markedly blocked Der-p–allergen sIgE complex binding to B cells, inhibited basophil activation, and markedly reduced the production of interleukin (IL)-5, IL-13, IL-17, and tumor necrosis factor-α by peripheral blood mononuclear cells. ConclusionSCIT-induced Der-p sIgG, sF(ab')2, and sFab antibodies may block the formation of Der-p–sIgE complexes and may serve as a potential allergen-targeted biologics candidate for the treatment of allergic asthma. Clinical Trial RegistrationThis study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University and registered in the Chinese Clinical Trial Registry (ChiCTR-OOC-15006207, https://www.chictr.org.cn/enindex.aspx).

Allergic Rhinitis and House Dust Mite Sensitization Determine Persistence of Asthma in Children

ObjectiveTo specify clinical and immunological parameters of the mechanisms, which may lead to development of persistent asthma, or regression of the disease symptoms.MethodsEighty children with childhood asthma, diagnosed in the past by using the modified Asthma Predicted Index (mAPI), were divided into two groups: remission group and persistent group. There were 3 study visits (baseline, at 6 mo, and at 12 mo). Clinical remission of asthma was defined as the absence of asthma symptoms for at least 12 mo without treatment. The patients could switch from one group to another during the 12 mo of follow-up. Clinical, inflammatory, and immunoregulatory predictors of asthma remission/persistence were analyzed.ResultsThe presence of mAPI criteria as well as house dust mite (HDM) allergy and allergic rhinitis at 7–10 y, were associated with a reduced prevalence of asthma remission. The increased eosinophil blood count in mAPI criteria was associated with a lower expression of CD25 positive cells. HDM allergy was associated with a higher fractional exhaled nitric oxide (FeNO) level (p = 0.0061) and higher expression of CD25CD71 (p = 0.0232). Allergic rhinitis was associated with a higher expression of PPAR (p = 0.0493) and CD25CD71 (p = 0.0198), and lower expression of glycoprotein A repetitions predominant (GARP).ConclusionsPersistence of childhood asthma was largely determined by the presence of allergic rhinitis and sensitization to HDM. Additionally, API criteria but not immunoregulation processes, were related to asthma persistence.

The SQ HDM SLIT-Tablet is safe and well tolerated in patients with House Dust Mite allergic rhinitis with or without asthma: A "real-life" French study.

BackgroundThe SQ House Dust Mite (HDM) SubLingual ImmunoTherapy (SLIT)‐Tablet (Acarizax) is the only allergen immunotherapy authorized by European regulatory authorities to treat HDM‐induced allergic asthma (AA) that is not well‐controlled by inhaled corticosteroids and associated with mild‐to‐severe HDM allergic rhinitis (AR). The aim of this study was to add evidence on the safety of the SQ HDM SLIT‐Tablet in patients with AR, alone or with AA, under real‐life conditions.MethodsThis was a French “real‐life”, multicenter, non‐comparative, longitudinal, prospective study. It included patients initiating the SQ HDM SLIT‐Tablet for either persistent moderate‐to‐severe HDM AR or AA not well‐controlled by inhaled corticosteroids and associated with mild‐to‐severe HDM AR. Adverse Events (AEs) were collected at the first intake and throughout the study. Logistic regression was used to compare safety according to asthma control before treatment initiation.ResultsBetween May 09, 2018 and May 29, 2019, 1526 patients were enrolled at 185 sites and 1483 were included in the safety population (SAF). Of them, 33.6% had suspected clinical manifestations of AA. Asthma was uncontrolled for 18.2% of the patients, partially controlled for 27.9% and well‐controlled for 53.8%. Overall, 31.9% of the SAF patients experienced at least one AE. The percentage of patients with AEs was 29.9% among patients with AR alone and 35.9% among those with AA (p = 0.0193). No significant difference was observed in the rate of AE or SAE depending on asthma control at inclusion (2.2% of SAEs reported for patients with uncontrolled asthma, 1.4% for partly controlled and 1.1% for well‐controlled).ConclusionsThe overall results indicate a good SQ HDM SLIT‐Tablet safety profile consistent with that reported in previous studies, regardless of asthma control.

Correlation between sensitization to house dust mite major allergens, age, and symptoms in Japanese house dust mite allergic subjects

Der p 23 has recently been recognized as a new house dust mite (HDM) major allergen that may be linked to the development of asthma in HDM allergic patients. This study aimed to investigate the frequency of sensitization to HDM major allergen components including Der p 23 and to examine the correlation between HDM-sensitization and AR symptom score in Japanese HDM allergic rhinitis (AR) patients without allergic asthma.Serum samples (n = 120) collected from Japanese HDM AR patients (12 to 64 years) without asthma were assessed for allergen-specific IgE (s-IgE) by ImmunoCAP (Dermatophagoides pteronyssinus (D. pteronyssinus; Der p) extract, Der p 23) or immunosolid-phase allergen chip (Der p 1, Der p 2).Japanese HDM AR patients without asthma showed a high prevalence of allergic sensitization to the HDM major allergens Der p 1 (94.2%), Der p 2 (97.5%) and Der p 23 (71.7%). No difference in the prevalence was detected for Der p 1 and Der p 2 s-IgE among three age groups. However, the prevalence of Der p 23 s-IgE was significantly higher in the younger group compared to the elderly group. No significant correlation was found between AR symptom scores and concentration of s-IgE towards Der p extract and any of the three HDM major allergens.Although the prevalence of sensitization towards D. pteronyssinus major allergens is high in Japanese AR patients without asthma, there was no correlation between allergen specific IgE including IgE towards Der p 23 and AR symptom in this population.

Post-Marketing Survey Evaluating the Safety and Efficacy of the SQ House Dust Mite (HDM) Sublingual Immunotherapy-Tablet in Japanese Patients with HDM-Induced Allergic Rhinitis (Stratified analysis by 18 years, 2016-2020)

The SQ house dust mite (HDM) sublingual immunotherapy (SLIT) tablet (10,000 JAU, Torii, Japan/6 SQ-HDM, ALK, Denmark) has been available for HDM allergic rhinitis (AR) in Japan since 2015. This post-marketing surveillance investigates the safety and efficacy of 3 years of treatment with the SQ HDM SLIT-tablet.

Clinical efficacy of sublingual immunotherapy for house dust mite-allergic rhinitis with sleep disturbances

Clinical efficacy of sublingual immunotherapy for house dust mite-allergic rhinitis with sleep disturbances

Der p 1 Disrupts the Epithelial Barrier and Induces IL-6 Production in Patients With House Dust Mite Allergic Rhinitis.

Background: Dermatophagoides pteronyssinus 1/2 (Der p 1/Der p 2) are regarded as important allergens of house dust mite (HDM). However, the effect of both products on the epithelial barrier and immune response of patients with and without HDM allergic rhinitis (AR) remains unclear.Methods: Air–liquid interface (ALI) cultured human nasal epithelial cells (HNECs) derived from control subjects (non-AR) (n = 9) and HDM-AR patients (n = 9) were treated with Der P 1 and Der P 2, followed by testing the transepithelial electrical resistance (TEER), paracellular permeability of fluorescein isothiocyanate (FITC)-dextrans and immunofluorescence of claudin-1 and ZO-1. Interleukin-6 (IL-6) production was evaluated by ELISA.Results: Der p 1 reduced TEER significantly in a transient and dose-dependent manner in HNEC-ALI cultures from HDM-AR and non-AR patients, whilst the paracellular permeability was not affected. TEER was significantly reduced by Der p 1 at the 10-min time point in HDM-AR patients compared to non-AR patients (p = 0.0259). Compared to no-treatment control, in HNECs derived from HDM-AR patients, Der p 1 significantly cleaved claudin-1 after 30 min exposure (72.7 ± 9.5 % in non-AR group, 39.9 ± 7.1 % in HDM-AR group, p = 0.0286) and induced IL-6 secretion (p = 0.0271).Conclusions: Our results suggest that patients with HDM-AR are more sensitive to Der p 1 than non-AR patients with increased effects of Der p1 on the mucosal barrier and induction of inflammation, indicating an important role for Der p1 in sensitization and HDM-AR development.

Epicutaneous Allergen Administration with Microneedles as a Novel Method of Immunotherapy for House Dust Mite (HDM) Allergic Rhinitis.

Epicutaneous immunotherapy (EPIT) is being studied as a method for treating allergic rhinitis because of skin immunology, user convenience and enhanced patient compliance. However, the use of EPIT is limited because of the very low skin permeability of the allergen. In this study, the limitations of EPIT were overcome by using sophisticated delivery with microneedles. The immunological efficacy of this method was studied in a murine model of house dust mite (HDM) allergic rhinitis. The length of the microneedles was 400μm, and the coating formulation containing HDM was locally distributed near the end of the microneedle tips. The change of distribution of FITC-dextran in porcine skin in vitro was observed over time using a confocal microscope. The effect of immunotherapy in the allergic rhinitis model, sensitized by HDM-coated microneedles (HDM MNs), was observed according to the amount of HDM applied. The microneedles delivered the coating formulation with precision into the porcine skin layer, and the coated formulation on the microneedles was all dissolved in the porcine skin in vitro within 20min of administration and then gradually diffused into the skin layer. When HDM MNs were administered to mice, a 0.1-μg dose of HDM provided the most effective immunization, and improved efficacy was shown between 0.1- and 0.5- μg doses of HDM. Effective immunotherapy can be achieved by precision delivery of the allergen into the skin layer, and microneedles can provide effective immunological therapy by delivering the appropriate amount of allergen.

A Real-Life One-Year Non-Interventional Study Assessing Safety, Tolerability, and Treatment Outcome of the SQ HDM SLIT-Tablet (Acarizax®) in House Dust Mite Allergic Rhinitis With or Without Asthma.

IntroductionThe aim of this study was to investigate the safety profile, tolerability, and outcome of the SQ® house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet after 1 year of treatment in clinical practice among adults with HDM-related allergic rhinitis (AR) ± allergic asthma (AA).MethodsIn a non-interventional multicenter, observational study, patients were followed at 3 visits for 1 year. Adverse events (AE) were recorded at all visits. Patients graded their allergic symptoms as none, mild, moderate, or severe, and recorded AR and AA medication use. Asthma symptom control was assessed according to the Global Initiative for Asthma (GINA).ResultsOne hundred and ninety-eight patients were included; 115 (58%) had AR without asthma and 83 (42%) had both AR and AA. One hundred and sixty-six (84%) patients completed the study. Eighty percent of patients experienced an AE: 151 (75%) AEs were mild, 42 (21%) moderate, and 4 (2%) severe. Three patients (1.5%) reported four events that were considered serious (SAEs). One SAE was considered possibly treatment-related. No anaphylactic reactions occurred. The proportion of patients experiencing allergy symptom reductions by at least one step were 75% (nasal), 62% (eye), 16% (skin), and 13% (other symptoms); 75% of patients with AA experienced a decrease of at least one step in bronchial symptoms. AR medication and inhaled corticosteroids were statistically significant reduced.ConclusionThe SQ HDM SLIT-tablet was safe and well tolerated; the type, frequency, and severity of AEs resembled what RCTs have previously demonstrated. As explorative endpoints, statistically significant reductions in AR and AA symptoms and medication use were seen along with improved asthma control after 1 year of treatment, implying that clinically meaningful changes were seen after 1 year of treatment with the SQ HDM SLIT-tablet.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41030-021-00150-z.

Moving Forward In Health Disparities: Aqueous Intradermal Immunotherapy

Mites (Dp/Df and Blomia tropicalis) are the major allergens in the tropics. Subcutaneous Immunotherapy (SCIT), hallmark of the allergy specialty, is an expensive effective tool for house dust mite allergic rhinitis (AR). Intradermal administration of low-dose mite allergens provides a cost-effective alternative for the impoverished majorities in tropical settings. Forty-three AR children (ages 4-18) attending an allergy clinic were offered intradermal immunotherapy. Only 25 with a Total Nasal Symptom Score (TNSS) >100 points were recruited and 17 completed one-year treatment. Injections consisted of a non-incremental volume of 0.05ml containing 50ng of Dp/Df major allergens and 120ng of Blomia tropicalis allergens. Shots were given following a 3-month schedule: once weekly for the first 3 months, later bi-weekly, then every 3 weeks and finally, monthly until a year’s completion. TNSS and fVAS were registered throughout the treatment year. IgG4 and IL10 serum levels along with QoL questionnaire, were evaluated before and after treatment. Qualitative scores TNSS, fVAS and QoL significantly improved (p<0.05): 8.58±0.86 vs 4.7±3.0 points, 6.0±1.5 vs 3.2±1.4 points, 35.0±11.4 vs 8.3±4.8 points, respectively. Quantitative results for IL-10, Dp/Df IgG4 and Blomia tropicalis IgG4 significantly increased (p<0.05): 3.61±4.2 vs 18.5±15.1 IU/ml, 2.07±1.8 vs 16.2±13.4 IU/ml, 0.11±0.11 vs 12.69±13 IU/ml, respectively. Cost per shot was estimated at less than USD 10 cents, making this approach a significant cost-saving strategy. Only mild local reactions were observed. Clinical improvement/laboratory responses were attained with this novel intradermal cost-effective technique. Health disparities concerning allergen immunotherapy might find, if reproduced, a step forward.

Anaphylaxis to Agaricus bisporus ingestion

ABSTRACTA 33-year-old male with house dust mite allergic rhinitis and asthma reported an episode of facial and lip angioedema, dyspnea, cough and dysphagia at the age of 25, minutes after eating a mushroom ( Agaricus bisporus ) pizza. He denied any drug intake, hymenoptera stings or other possible triggers, and no identifiable cofactors were present. Since then he avoided all types of mushrooms, however an accidental contact occurred with mushroom sauce that resulted in angioedema of the lip within minutes. The allergy workup included measurements of total IgE and specific IgE to mushroom, and skin prick test to aeroallergens sources, possible food allergen sources and mushroom extract, a prick to prick test with raw and cooked A. bisporus , in addition to a SDS-PAGE and immunoblotting assay. The study revealed a specific IgE to mushroom of 0.76kUA/L positive skin prick test to mushroom extract, and prick to prick test positive to white and brown A. bisporus (raw and cooked). The immunoblotting identified two IgE binding proteins with 10kDa and 27kDa. We report a case of A. bisporus anaphylaxis probably due to primary mushroom sensitization. We detected two IgE-reactive proteins with 10kDa and 27kDa as possible culprit allergens.