Novel monoclonal antibodies against house dust mite allergen Der p 21 and their application to analyze allergen extracts.

Background: Allergen extracts and recombinant allergens are used in allergy diagnostics and immunotherapy. Since allergen extracts from different manufacturers lack proper standardization regarding their composition, monoclonal antibodies (MAbs) against specific allergen components can be used for their identification and quantification in allergen extracts. This study aimed to generate MAbs against allergen Der p 21 of Dermatophagoides pteronyssinus for the analysis of allergen extracts. Methods: Recombinant Der p 21 was expressed in E. coli and purified using affinity chromatography. MAbs against Der p 21 were generated using hybridoma technology. House dust mite (HDM) allergen extracts were analyzed using the newly developed sandwich enzyme-linked immunosorbent assay, Western blotting and microarray immunoassay. Results: MAbs raised against recombinant Der p 21 were characterized in detail and proven to be reactive with natural Der p 21. Highly specific sandwich enzyme-linked immunosorbent assay for the quantification of Der p 21 was developed and optimized. The allergen was detected and its concentration was determined in only three of six analyzed HDM allergen extracts from different manufacturers. Conclusion: HDM analysis by MAb-based immunoassays shows their differences in allergen composition. The results demonstrate the importance of allergen-specific MAbs as a tool for the characterization of allergen extracts and the need for their appropriate standardization before their use for allergy diagnostics or immunotherapy.

IgG from Dermatophagoides pteronyssinus (Der p)-atopic individuals modulates non-atopic thymic B cell phenotype (alfa-4/beta-7) and cytokine production (IFN-γ, IL-9, and IL-10) with direct membrane interaction.

Studies about thymic B cells are scarce in the literature, but it was suggested that they can exert modulatory and regulatory functions on the immune system. Thymic B cells can play some role in regulating the most frequent allergic background worldwide, the atopy induced by the mite Dermatophagoides pteronyssinus (Der p). Here, we aimed to evaluate if the polyclonal IgG repertoire produced by Der p-atopic individuals can influence the homing and cytokine profile of human thymic B derived from non-atopic children aged less than seven days. With this purpose, we produced polyclonal IgG formulations and cultivated human thymocytes in their presence. We also assessed IgG subclasses and the direct interaction of IgG with thymic B cell membranes. Our results could demonstrate that Der p-atopic IgG could not reduce the expression of α4ß7 homing molecule as observed in response to the other IgG formulations and could reduce the frequency of IFN-γ- and IL-9-producing thymic B cells compared to the mock condition. Der p-atopic IgG could also induce thymic IL-10-producing B cells compared to control conditions. The IgG derived from Der p-atopic individuals failed to diminish the population of IL-13-producing thymic B cells, unlike the reduction observed with other IgG formulations when compared to the mock condition. All IgG formulations had similar levels of IgG subclasses and directly interacted with thymic B cell membranes. Finally, we performed experiments using peripheral non-atopic B cells where IgG effects were not observed. In conclusion, our observation demonstrates that IgG induced in allergic individuals can modulate non-atopic thymic B cells, potentially generating thymic B cells prone to allergy development, which seems to not occur in mature B cells.

House dust mite SCIT reduces asthma risk and significantly improves long-term rhinitis and asthma control-A RWE study.

BACKGROUND: The German Therapy Allergen Ordinance (TAO) triggered an ongoing upheaval in the market for house dust mite (HDM) allergen immunotherapy (AIT) products. Three HDM subcutaneous AIT (SCIT) products hold approval in Germany and therefore will be available after the scheduled completion of the TAO procedure in 2026. In general, data from clinical trials on the long-term effectiveness of HDM AIT are rare. We evaluated real-world data (RWD) in a retrospective, observational cohort study based on a longitudinal claims database including 60% of all German statutory healthcare prescriptions to show the long-term effectiveness of one of these products in daily life. Aim of this analysis was to provide a per product analysis on effectiveness of mite AIT as it is demanded by international guidelines on AIT. METHODS: Subjects between 5 and 70 years receiving their first (index) prescription of SCIT with a native HDM product (SCIT group) between 2009 and 2013 were included. The exactly 3:1 matched control group received prescriptions for only symptomatic AR medication (non-AIT group); the evaluation period for up to 6 years of follow-up ended in February 2017. Study endpoints were the progression of allergic rhinitis (AR) and asthma, asthma occurrence and time to the onset of asthma after at least 2 treatment years. RESULTS: In total, 892 subjects (608 adults and 284 children/adolescents) were included in the SCIT group and 2676 subjects (1824 adults and 852 children/adolescents) in the non-AIT group. During the follow-up period after at least 2 years of SCIT, the number of prescriptions in the SCIT group was reduced by 62.8% (p < .0001) for AR medication and by 42.4% for asthma medication (p = .0003). New-onset asthma risk was significantly reduced in the SCIT vs non-AIT group by 27.0% (p = .0212). The asthma-preventive effect of SCIT occurred 15 months after start of the treatment. In the SCIT group, the time to onset of asthma was prolonged compared to the non-AIT group (p = .0010). CONCLUSION: In this first product based RWD analysis on SCIT with a native HDM product, patients aged 5 to 70 years benefited from AIT in the long term in terms of reduced progression of AR and asthma after at least 2 years of treatment. The effects seemed to last for up to 6 years after treatment termination. A significantly reduced risk of asthma onset was observed, starting after 15 months of treatment.

[Molecular diagnostic strategies and management of dust mite allergy].

Dust mites are one of the most important allergens, widely distributed around the world, especially in household environments. Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis are the most common species of dust mites. There are more than 35 known sensitization components of dust mites, among which Der p 1, Der p 2 and Der p 23 are the major components. Clinically, allergen skin test and serum specific immunoglobulin E (sIgE) detection are widely used in the preliminary diagnosis of dust mite allergy. However, these methods cannot accurately identify specific dust mite sensitization components. Considering that there are significant differences in the allergenic components of dust mites in different regions and populations, component-resolved diagnosis of dust mite is particularly important in accurately determining the allergenic components. This is not only of guiding significance for allergen avoidance, but also important for determining the immunotherapy regimen for dust mites. In order to strengthen the understanding of the molecular diagnosis of dust mites and promote the integration of allergy science in China with the international standards, this article interprets the "Allergy Molecular Allergology User's Guide 2.0" published recently by the European Academy of Allergy and Clinical Immunology.

Increase in the prevalence of follicular regulatory T cells correlates with clinical efficacy of sublingual immunotherapy with house dust mites.

BACKGROUND: Allergic rhinitis (AR) impairs quality of life and affects nearly 40% of the Japanese population. Sublingual immunotherapy (SLIT) is the disease-modifying treatment for AR, but requires the selection of a biomarker associate with clinical efficacy in patients with AR who are treated with SLIT. The present study sought to examine objective biomarkers used for assessing the clinical efficacy of SLIT. METHODS: The authors examined the effects of 1 year of SLIT treatment with house dust mites (HDMs) using peripheral blood mononuclear cells (PBMCs) and serum from patients with AR. The prevalences of follicular regulatory T (Tfr), type 2 follicular helper T (Tfh2), type 2 helper T (Th2), conventional regulatory T (Treg), and type 1 regulatory T (Tr1) cells were examined by flow cytometry. Serum concentrations of HDM-specific IgA, IgE, and IgG4 antibodies, and HDM-induced production of interleukin (IL) 5 and IL-10 from cultured PBMCs were evaluated by enzyme-linked immunosorbent assay. RESULTS: Following 1 year of SLIT, the prevalences of Tfr, conventional Treg, and Tr1 cells were significantly increased, whereas that of Th2 cells and Tfh2 cells were significantly decreased; the serum concentration of HDM-specific IgG4 was significantly increased; and HDM-induced production of IL-5 from PBMCs was significantly decreased, while that of IL-10 was significantly increased. The increase in the prevalence of Tfr cells after SLIT correlated positively with the improvement of clinical symptom scores. CONCLUSION: An increase in Tfr cells may play an important role in SLIT, and may be a useful indicator for the clinical efficacy of SLIT.

Efficacy and safety of intratonsillar immunotherapy for allergic rhinitis: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: A lower adherence rate existed in patients receiving allergen-specific immunotherapy due to its lengthy period and adverse effects even though it is the only curative treatment for IgE-mediated allergies. Therefore, exploring innovative allergen-specific immunotherapy routes is necessary. OBJECTIVE: To explore the efficacy and safety of the intratonsillar injection of house dust mite (HDM) extract in patients with HDM-induced allergic rhinitis (AR). METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 80 patients with HDM-induced AR were randomized to receive 6 intratonsillar injections with HDM extract or placebo in 3 months. The total nasal symptom score (TNSS), visual analogue scale of nasal symptoms, combined symptom and medication score, mini rhinoconjunctivitis quality of life questionnaire, and serum allergen-specific IgG4 to Dermatophagoides pteronyssinus were all monitored at baseline and 3 months, 6 months, and 12 months after the treatment was finished. The intent-to-treat and per-protocol set (PPS) are both analyzed. RESULTS: The primary end points TNSS and ΔTNSS were improved significantly at 3 months after the patients with AR finished a 3-month 6-injection intratonsillar immunotherapy compared with those in the placebo treatment in both intent-to-treat and PPS. Results of visual analogue scale, combined symptom and medication score, and mini rhinoconjunctivitis quality of life questionnaire were also improved significantly at 3 months after the treatment in PPS. However, the improvement effect of intratonsillar immunotherapy at 6 and 12 months was limited and uncertain based on the data. The increase of serum Der p IgG4 in the active group was significantly higher than that in the placebo group at 3, 6, and 12 months after the treatment was finished. Adverse events were monitored, and no systemic adverse reactions were observed. CONCLUSION: The clinical trial revealed that intratonsillar injection with HDM extract was safe and effective in patients with AR. Optimizing the protocol and allergen formulations is expected to increase and maintain the efficacy of this novel approach. TRIAL REGISTRATION: https://www.chictr.org.cn/index.html, identifier: ChiCTR-TRC-13003600.

Update on the role of genetic factors, environmental factors and allergens in canine atopic dermatitis.

BACKGROUND: Canine atopic dermatitis (cAD) is a common, complex and multifactorial disease involving, among others, genetic predisposition, environmental factors and allergic sensitisation. OBJECTIVE: This review summarises the current evidence on the role of genetic and environmental factors and allergic sensitisation in the pathogenesis of cAD since the last review by ICADA in 2015. MATERIALS AND METHODS: Online citation databases and proceedings from international meetings on genetic factors, environmental factors and allergens relevant to cAD that had been published between 2015 and 2022 were reviewed. RESULTS: Despite intensive research efforts, the detailed genetic background predisposing to cAD and the effect of a wide range of environmental factors still need more clarification. Genome-wide association studies and investigations on genetic biomarkers, such as microRNAs, have provided some new information. Environmental factors appear to play a major role. Lifestyle, especially during puppyhood, appears to have an important impact on the developing immune system. Factors such as growing up in a rural environment, large size of family, contact with other animals, and a nonprocessed meat-based diet may reduce the risk for subsequent development of cAD. It appears that Toxocara canis infection may have a protective effect against Dermatophagoides farinae-induced cAD. House dust mites (D. farinae and D. pteronyssinus) remain the most common allergen group to which atopic dogs react. Currently, the major allergens related to D. farinae in dogs include Der f 2, Der f 15, Der f 18 and Zen 1. CONCLUSIONS AND CLINICAL RELEVANCE: Canine atopic dermatitis remains a complex, genetically heterogeneous disease that is influenced by multiple environmental factors. Further, well-designed studies are necessary to shed more light on the role of genetics, environmental factors and major allergens in the pathogenesis of cAD.

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.

Open trial of recombinant Der f 2 pullulan-conjugated immunotherapy in cats.

BACKGROUND: Allermmune HDM (Zenoaq) is a recombinant Dermatophagoides farinae 2 (Der f 2) pullulan-based immunotherapy vaccine whose efficacy on house dust mite allergic dogs has been demonstrated. There is no published information on its use in cats. OBJECTIVES: The objective of the study was to evaluate the safety and short-term effects of Allermmune HDM in Dermatophagoides farinae (Df)-sensitised cats. MATERIALS AND METHODS: Eleven cats diagnosed with atopic skin syndrome received Allermmune weekly for six weeks then monthly for three months (total duration 18 weeks). On Weeks 0, 6 and 18 clinical lesions were assessed by the Feline Dermatitis Extent and Severity Index (FEDESI); owners assessed pruritus with a 10-cm Visual Analog Scale (pVAS). Concurrent medication use was recorded. The allergen-specific immunoglobulin (Ig)E were measured before study inclusion with a commercial serological assay. RESULTS: There were no evident adverse effects. FEDESI and pVAS improved significantly after six weeks (p = 0.001 and p = 0.01, respectively). The pretreatment Df-specific IgE levels were significantly higher in the cats with improved clinical scores than in the cats with no clinical score change (p = 0.009). CONCLUSIONS AND CLINICAL RELEVANCE: Allermmune HDM may be safe in cats and has the potential to alleviate signs of atopic skin syndrome. Allergen-specific IgE levels may represent an efficacy marker. Controlled studies of longer duration and larger sample size are worth pursuing.

Genetic and T2 biomarkers linked to the efficacy of HDM sublingual immunotherapy in asthma.

BACKGROUND: Hypersensitivity to house dust mite (HDM) allergens is a common cause of allergic asthma symptoms and can be effectively treated with allergy immunotherapy (AIT). OBJECTIVE: To investigate whether genetic and type 2 (T2) inflammatory biomarkers correlate with disease severity in subjects with allergic asthma, and whether this can be modified by AIT. METHODS: MITRA (NCT01433523) was a phase III, randomised, double-blind, placebo-controlled trial of HDM sublingual immunotherapy (SLIT)-tablets in adults with HDM allergic asthma. Post hoc analyses of the study population (N=742) evaluated associations between T2 inflammatory (blood eosinophils, eosinophil cationic protein (ECP), total IgE and tryptase) and genetic (single-nucleotide polymorphisms, SNP) biomarkers (n=582) for the primary study endpoint (time to first moderate/severe asthma exacerbation). SNP associations were verified in HDM-positive subgroup from an independent 3-year Severe Asthma Research Programme (SARP3) subject cohort. RESULTS: An increased asthma exacerbation risk in subjects homozygous for SNP rs7216389 (chromosomal locus 17q12-21) was reduced (p=0.037) by treatment with HDM SLIT (HR=0.37 (95% CI 0.22 to 0.64), p<0.001). The associations between exacerbation risk and 17q12-21 SNPs were replicated in the SARP3 HDM-positive subgroup. High levels of T2 biomarkers were associated with increased risk of asthma exacerbations in the placebo group. HDM SLIT-tablet treatment reduced this risk (blood eosinophils: HR=0.50 (95% CI 0.30 to 0.85); ECP: HR=0.45 (95% CI 0.29 to 0.87); tryptase: HR=0.45 (95% CI 0.25 to 0.80)). The treatment effect was higher (p=0.006) for subjects with a higher number of elevated T2 biomarkers. CONCLUSIONS: HDM SLIT-tablet AIT is efficacious in HDM-sensitised asthma subjects with a genetic asthma predisposition and/or an underlying T2 endotype. TRIAL REGISTRATION NUMBER: NCT01433523.

Residual profiles and health risk of indoor allergens in China.

Exposure to indoor allergens is a principal risk factor for allergic diseases. However, most of the previous studies on indoor allergens focused on very limited kinds of allergens in China. Knowledge of the simultaneous exposure to multiple allergens is still lacking. In this study, the residual profiles of 8 allergens were investigated in 166 dust samples from 11 cities in China. The house dust mite allergens including Der p 1, Der f 1, and Der 2 were detected in the range of <0.02-283.83 µg/g dust. The concentrations of dog allergen Can f 1 and cat allergen Fel d 1 varied widely, from <0.84-22,896.46 µg/g dust for Can f 1 and from <0.02-6298.96 µg/g dust for Fel d 1. Cockroach allergen Bla g 2 was detected in 68% of the samples but at a low level with a maximum of 9.44 µg/g dust. Comparatively low detection frequencies were found for mouse allergen Mus m 1 as 37% and for fungi allergen Asp f 2 as 24%. The frequency of cleaning sheets/bedding was negatively correlated to the levels of house dust mite allergens. The presence of pets indoors was associated with higher levels of pet allergens and lower levels of house dust mite allergens and cockroach allergen. Risk evaluation reveals that at least 4 allergens were found in more than 80% of the rooms and more than 2 allergens with median/high risk were detected in 42% of the rooms, indicating that simultaneous exposure to multiple allergens is prevalent in China.

Long-Term Efficacy and Safety of Subcutaneous Immunotherapy in Monosensitized and Polysensitized Children With Allergic Rhinitis.

OBJECTIVE: To evaluate the efficacy and safety of dust mite subcutaneous immunotherapy (SCIT) in monosensitized and polysensitized children with allergic rhinitis (AR). STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center. METHODS: One hundred thirty children were enrolled and categorized into 2 groups: monosensitized to only dust mites and polysensitized to at least 1 additional allergen beyond dust mites. All patients received SCIT targeting dust mites for 3 years, followed by a 5-year monitoring period. The Total Nasal Symptom Score (TNSS), Symptom and Medication Score (SMS), Visual Analogue Scale (VAS), and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) were assessed before SCIT (T0); at 1 (T1) and 2 (T2) years of SCIT; immediately after SCIT (T3); and 2 years post-SCIT (T5). Safety was assessed based on adverse events (AEs). RESULTS: Fifty-one monosensitized and 50 polysensitized children completed the study. At T3, 47 monosensitized and 46 polysensitized children were effectively treated, with no significant between-group difference in efficacy (P > .05). The TNSS, SMS, VAS scores, and RQLQ score were significantly lower at T1, T2, T3, and T5 than at T0 in both groups (P < .05). The differences in the TNSS, SMS, VAS score, and RQLQ score between the 2 groups were nonsignificant at T0, T1, T2, and T3 (P > .05), but significant at T5 (P < .05). No serious AEs were reported. CONCLUSION: Monosensitized and polysensitized children exhibited similar beneficial efficacy and safety after 3 years of dust mite SCIT. Monosensitized children derived more benefits 2 years after discontinuation.

Effect of intralymphatic allergen-specific immunotherapy on house dust mite in a murine model of allergic rhinitis.

BACKGROUND: Intralymphatic immunotherapy (ILIT) is a promising alternative for the treatment of patients with allergic rhinitis, providing similar therapeutic efficacy to conventional allergen-specific immunotherapy (AIT). However, the allergic mechanism of ILIT is not completely known. AIM: The aim of this study was to determine the efficacy of ILIT in a house dust mite (HDM) mouse model of allergic rhinitis. METHODS: BALB/c mice were divided into four groups: G1, control without allergy; G2, allergy sensitized with HDM; G3, allergy with ILIT (starting with HDM 1.25 µg/mL); and G4, allergy with ILIT (starting with HDM 2.5 µg/mL). After the murine model of allergic rhinitis with HDM was established, mice were administered an intralymphatic injection through the inguinal lymph nodes with HDM. RESULTS: ILIT decreased serum total IgE level and eosinophil infiltration in the nasal mucosa. ILIT also decreased the expression levels of IL-13, IL-25, IL-33, IFN-γ, IL-6, and IL-17, and increased the expression of FoxP3(+) T reg cells. CONCLUSIONS AND SIGNIFICANCE: Our results suggest that ILIT regulates the specific immunotherapy immunologic mechanism by downregulating Th1, Th2, and Th17 cytokines and upregulating FoxP3(+) T reg cells in the HDM allergic mouse model.

House dust mite allergy in Malaysia: review of research gaps in the current scenario and the way forward.

The prevalence of house dust mite (HDM) allergy, especially in Asian countries with rapid urbanization, has been increasing. House dust mites thrive in places with relatively high humidity. With the combination of climate change, naturally high humidity, and urbanization, tropical countries like Malaysia are becoming a hotspot for HDM allergy fast. With a previously reported sensitization rate of between 60 and 80%, it is a worrying trend for Malaysia. However, due to incomplete and out-of-date data, as seen by the limited study coverage in the past, these numbers do not paint a complete picture of the true HDM allergy scene in Malaysia. This review briefly discusses the HDM fauna, the HDM sensitization rate, the common diagnosis and therapeutic tools for HDM allergy in Malaysia, and makes suggestions for possible improvements in the future. This review also highlights the need of more comprehensive population-based prevalence studies to be done in Malaysia, encompassing the three main HDMs-Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Blomia tropicalis-as the lack of up-to-date studies failed to give a clearer picture on the current scenario of HDM allergy in Malaysia. Future studies will be beneficial to the nation in preparing a better blueprint for the management and treatment of HDM allergy.

Dust mite component Analysis: Identifying key allergens components for effective immunotherapy in allergic rhinitis.

BACKGROUND: The aim of this study was to examine the frequency of sensitization to house dust mite (HDM) components among allergic rhinitis patients receiving subcutaneous immunotherapy (SCIT), and to assess the correlation between SCIT efficacy and specific IgE (sIgE) levels for allergenic HDM components. METHODS: Serum samples and clinical data were collected from 38 allergic rhinitis patients receiving HDM-SCIT at baseline and after 1 year of treatment. Effective treatment was defined as a therapeutic index (TI) of at least 50% after 1 year. Cytokine levels were analyzed using commercial ELISA kits, while serum total and specific IgE levels were determined by the fluoroenzymeimmunoassay technique. The ALLEOS 2000 magnetic particle chemiluminescence system was used to measure sIgE levels for Der f, Der p 1, Der p 2, Der p 10, and Der p 23. RESULTS: Allergic rhinitis patients undergoing HDM-SCIT had a high rate of allergic sensitization to the HDM major allergens Der p (100%), Der f (100%), Der p 1 (94.74%), Der p 2 (94.74%), and Der p 23 (36.84%). Patients who responded to SCIT had higher levels of IgE for HDM components at baseline, while those with ineffective treatment showed an opposite performance, particularly for Der p 1 (P＜0.05). After 1 year of treatment, effective and ineffective patients showed opposite trends in sIgE for dust mite components (decreased in effective patients, increased in ineffective patients). HDM-SCIT led to a significant reduction in IL-2, IL-4, IL-6, and EOS% (P＜0.05). IgE for Der p, Der f, Der p 1, Der p 2, and HDM sIgE were significantly positively correlated (P < 0.001). The correlation heatmap analysis based on changes in values reveals a negative correlation between CSMS score changes and sIgE for Der f and Der p 1, and a positive correlation with IL-2, IL-10, and TNF (P < 0.05). CONCLUSIONS: The molecular sensitization profiles during HDM-SCIT are variable and relate to treatment efficacy. Molecular diagnosis can assist allergists in identifying patients eligible for HDM-SCIT, thereby enhancing the treatment's clinical efficacy. Serum cytokine levels of IL-2, IL-4, IL-6，and EOS% may serve as useful biomarkers for monitoring HDM-SCIT efficacy.

Risk Factors for Acute Rhinosinusitis in Childhood Asthma.

INTRODUCTION: Specific pathogen infections associated with acute rhinosinusitis (ARS) in infants are risk factors for allergic asthma in adolescents. However, the risk factors for ARS onset remain largely unknown in asthmatic children. In this study, we aim to investigate the risk factors for ARS in childhood asthma. METHODS: This study retrospectively compared and analyzed the clinical characteristics of asthmatic children with (n = 194) or without ARS (n = 799). Univariate regression analyses were performed to identify ARS-associated risk factors in asthmatic children, and subsequent multivariate backward stepwise logistic regression analyses were performed to identify independent risk factors. RESULTS: The onset age, values of blood eosinophils (EOS) (%), and total IgE were significantly lower in patients with ARS than in those without ARS. Moreover, the proportions of patients allergic to Dermatophagoides pteronyssinus (d1) and Dermatophagoides farinae (d2) were significantly smaller in children with ARS (all p values <0.05). Univariate analyses showed that an older onset age, a higher body mass index, a higher value of blood EOS (%) were protective factors, while a higher value of blood lymphocytes (%) and a higher degree of sensitization to d1 and d2 were risk factors for ARS. Further backward stepwise multivariate logistic regression analyses confirmed that a younger onset age and allergic sensitization to d1 were independent risk factors for ARS in childhood asthma. CONCLUSION: Younger onset age and allergic sensitization to d1 are risk factors for the onset of ARS in childhood asthma, so allergen intervention should be performed as early as possible in asthmatic children.

[The efficacy and safety of standardized dust mite allergen subcutaneous immunotherapy in children with allergic rhinitis during treatment].

Objective: To evaluate the efficacy and safety of standardized dust mite allergen subcutaneous immunotherapy (SCIT) in children with allergic rhinitis (AR) during treatment. Methods: A total of 283 children with AR diagnosed with definite dust mite allergy and completed 2 to 3 years of SCIT who attended the Department of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, from August 2019 to October 2021 were included, including 205 males and 78 females, with a mean age of 10.8 years. The total nasal symptoms score (TNSS), symptom medication score (SMS), rhinoconjunctivitis quality of life questionnaire (RQLQ) and visual analogue scale (VAS) before and after 2 to 3 years' treatment were recorded, and the differences before and after treatment were compared. Adverse reactions during SCIT were recorded to evaluate its safety. SPSS 22.0 software was used for statistical analysis. Results: The overall effectiveness rate during SCIT in 283 children with AR was 89.4% (253/283). Compared with baseline, all symptom scores, medication scores and quality of life scores were significantly lower after 2 to 3 years of SCIT (all P<0.05). Further group comparisons showed positive efficacy in patients with different clinical characteristics, including age, gender, smoking status, family history of AR, symptom severity, mono-or poly-allergy, and second immunization, with no statistically significant differences between groups (all P>0.05). A total of 12 735 injections were administered during the SCIT, and a total of 213 (1.67%) injections of local adverse reactions occurred, mainly in the initial treatment phase, and the diameter of the local air mass was mostly 5 to 20 mm; 71 (0.56%) injections of systemic adverse reactions occurred, mainly in the initial treatment phase, and most of them were grade 1 reactions with no serious systemic adverse reaction such as shock. Conclusion: Standardized dust mite SCIT has a good safety profile and definite efficacy in treating AR children with different clinical characteristics. It can significantly improve all symptoms, reduce the use of symptomatic drugs and improve their quality of life.

Safety and effectiveness of a 300 IR house dust mite sublingual tablet: descriptive 4-year final analysis of a post-marketing surveillance in Japan.

Background: Data are limited for clinical outcomes with house dust mite (HDM) allergen immunotherapy beyond 2 years' observation. Materials & methods: A post-marketing drug-use survey assessed the safety and effectiveness of the 300 index of reactivity (IR) HDM tablet during use for up to 4 years in Japan. Results: 538 patients were evaluable for safety and 383 for effectiveness. Most adverse drug reactions (ADRs) occurred early and were local reactions; 5.6% of 249 total events were reported during years 2 to 4 as new ADRs after the interim analysis. The CAP-RAST score was identified as a potential risk factor for ADRs. The proportion of evaluable patients with severe allergic rhinitis symptoms decreased from 46.4% at baseline (n = 317) to 1.0% at 4 years (n = 104). Patients (n = 16) who discontinued 300 IR HDM tablet due to symptomatic improvement had sustained improvement relative to baseline 1 to 2 years later. Conclusion: Long-term use of the 300 IR HDM tablet is safe and effective.

The 300 index of reactivity house dust mite (HDM) sublingual tablet (Actair^®) is a treatment option for people with HDM allergy. A Japanese study investigated the safety and effectiveness of the HDM sublingual tablet during its use for up to 4 years. Less than a third of patients (29%) reported adverse effects, mainly itching or irritation in the mouth. The percentage of patients with no allergic rhinitis symptoms increased from 0.3% before treatment to 57.7% after 4 years of use. The percentage of patients who perceived that their allergic rhinitis had improved 'substantially' compared with before treatment increased from 22.3% at 6 months to 73.5% at 4 years. Patients who ended treatment with the HDM sublingual tablet because their symptoms had improved continued to perceive benefit 1 to 2 years later. Clinical Trial Registration: University hospital Medical Information Network (UMIN) Clinical Trials Registry identifier: UMIN000042840.

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.