Towards real life exposure: nasal epithelial cell stimulation with pollen particle aerosols.

The Therapy Allergen Ordinance (TAO) aims to migrate allergen immunotherapy (AIT) products for the treatment of common allergies, which were previously marketed in Germany as named patient products (NPPs), into authorized products provided their quality, efficacy, and safety are adequately shown. The TAO applies to all NPPs containing active ingredients based on the following allergen sources: house dust mites, bee venom, wasp venom, pollen from sweet grasses (excluding maize), birch, alder, or hazel. The last product-specific deadlines granted under the TAO for the submission of clinical data relevant to the marketing authorization process will expire in 2026. The subsequent final assessment of the updated marketing authorization application (MAA) is carried out by the competent authority, the Paul-Ehrlich-Institut. During this period of processing by the competent authority, the products remain marketable until a decision regarding the MAA has been reached. Currently (as of August 08, 2025), 40 AIT products are still marketable under the transitional provisions of the TAO (10 preparations for the treatment of allergies to house dust mites, 10 against tree pollen allergies, 16 against grass pollen allergies, and 4 mixed preparations containing non-homologous allergen groups). For 8 of these products, pharmaceutical companies have initiated the withdrawal of MAA as of October 01, 2025 or January 31, 2026, respectively. Prior to the final assessment of the updated MAAs, the competent authority is unable to make any public statements as to whether the individual applications for the remaining 32 products under the transitional provision will be concluded positively with the granting of the marketing authorization or its rejection. With the rejection of a marketing authorization, the product-specific marketability ends immediately, i.e., there is no additional sell-off period for the TAO products concerned. If a marketing authorization is granted, the marketability of the specific product is perpetuated.

Component-resolved diagnostics study on nut sensitization and cross-reactivity in China.

Comparing alder, birch and grass pollen concentrations derived from spatiotemporal statistical and dispersion models across Switzerland

Meteorological changes can influence the type and concentration of allergenic pollen in the atmosphere. This study aimed to investigate the relationship between the diversity of pollen sensitivity based on skin prick test (SPT) reactions and meteorological changes over the past 10 years in Konya, Türkiye. A total of 23,111 patients who underwent skin prick testing (SPT) between January 2015 and December 2024 were included in the study. Meteorological data, including temperature, sunlight exposure, relative humidity, rainfall, and wind speed, were obtained from the 8th Regional Directorate of Meteorology. Our analysis revealed significant relationships between meteorological parameters and pollen sensitivity. Sunlight duration was positively correlated with sensitivity to tree pollen (r = 0.608, p < 0.001). Wind speed was positively correlated with sensitivity to tree pollen (r = 0.433, p = 0.002) but negatively correlated with sensitivity to Chenopodium (r = -0.353, p = 0.013). Humidity was positively correlated with sensitivity to weed and grass pollen (r = 0.367, p = 0.022; r = 0.305, p = 0.033) and negatively correlated with sensitivity to tree pollen (r = -0.605, p < 0.001). Temperature was positively correlated with sensitivity to Artemisia vulgaris (r = 0.317, p = 0.034) and negatively correlated with sensitivity to weed pollen (r = -0.734, p < 0.001). Rainfall was negatively correlated with sensitivity to grass pollen (r = -0.296, p = 0.039), tree pollen (r = -0.850, p < 0.001), and Chenopodium (r = -0.408, p = 0.004). Our results revealed intricate interactions between pollen sensitivity and meteorological parameters. Notably, rainfall consistently exhibited a negative correlation with specific pollen types, suggesting a potential mitigating effect on pollen-related sensitization. These findings underscore the importance of considering meteorological variability in the management and prediction of allergic diseases.

Adherence to Grass Pollen Allergen Immunotherapy and Allergy Medication Use in Patients With Allergic Rhinitis.

Current treatments fall short in managing allergic rhinitis (AR), emphasizing the need for additional strategies. Beneficial bacteria application shows promise in AR; however, most studies focus on oral probiotic administration without monitoring the applied strains in the upper respiratory tract (URT) and their local effects. In this randomized, double-blind, placebo-controlled trial, the probiotic Lacticaseibacillus rhamnosus GG was administered via chewable tablets in seasonal AR patients, randomized to probiotic (n = 33) or placebo (n = 31) groups. Per-protocol analysis of the URT microbiome, immune markers, and AR symptoms was performed. L. rhamnosus GG trafficked from chewables to the oropharynx (77%, P = 0.02) and nasopharynx (41%, P < 0.0001). Control of self-reported AR symptoms via validated questionnaires under grass pollen exposure was observed after 2 weeks of probiotic administration and not upon placebo. A local decrease in salivary interleukin-4 (P < 0.05) and nasal IL-13 (P < 0.0001) was observed in the probiotic group. These data indicate that L. rhamnosus GG chewables can target the URT and exert local effects on key allergy cytokines after temporal probiotic engraftment.IMPORTANCEAllergic rhinitis (AR) or hay fever is a highly prevalent condition, impacting nearly half the population in some countries. Supplementation of beneficial bacteria or probiotics has gained increasing attention in AR, and a key innovative way to do this is direct administration to the upper airways. Our study shows for the first time that the model probiotic strain Lacticaseibacillus rhamnosus GG can traffic to the nose in AR patients when administered via a slow-releasing chewable tablet. This trafficking is associated with local benefits in the airways, including on grass pollen-induced nasal symptoms and allergy-related cytokines.

Sensitization to inhalant allergens is a major factor in the development of allergic diseases. Despite this, few studies have comprehensively analyzed age- and sex-specific patterns within defined populations. This study aimed to investigate the prevalence and distribution of sensitization to inhalant allergens in different demographic groups of the Lithuanian population using molecular diagnostics. We retrospectively reviewed molecular allergy profiles of 658 patients tested with the ALEX2 macroarray between 2020 and 2022. Sensitization to inhalant allergen components was assessed and compared across three age groups (<18, 18–44, >44 years) and by sex. Sensitization to at least one inhalant allergen was observed in 62.16% of patients. Rates were significantly higher in males compared to females, particularly in the reproductive-age group (p = 0.0167). Children exhibited the highest prevalence, which declined with age. Tree pollen, pet dander, grass pollen, and dust mites were the dominant allergen groups. Boys were more often sensitized than men, and girls more often than women. Male patients showed higher sensitization to most allergens, except dust mites and weeds in certain female subgroups. Distinct age- and sex-related differences in sensitization patterns were identified. These results emphasize the importance of demographic factors in allergy diagnostics and highlight the need for region-specific sensitization data to inform clinical care and public health strategies.

Background: The CAMS Regional System provides crucial, reliable pollen forecasts for allergenic pollen types. These robust predictions support the scientific and medical communities, aiding in the diagnosis, evaluation, and protection of allergic populations. So, the main goal of this study was to evaluate which model, or models best represent and simulate the olive and grass pollen data of the Évora region in the years 2021 to 2024. Results: The results showed that there are statistically significant differences between the data of the models and between the years for each of the pollen types considered. These differences were not just in pollen concentrations; they also appeared in characteristics of the pollen season, like its duration, maximum peak concentration, start date and exposure level. According to Taylor diagrams, applying moving average for normalized data, it was shown that MOCAGE best represents and simulates olive concentration data. For grass pollen SILAM, EURAD-IM and MOCAGE were the best performers. Conclusions: CAMS data can enhance the quality of life of the allergic population, as well as support the scientific and medical community to improve, assist and create mitigation measures that reduce exposure and consequently significantly reduce the occurrence of allergic disease.

European guidelines recommend using a standardized baseline series of skin prick test (SPT) allergens for the diagnosis of airway allergies. In addition, local adaptation and/or extension of test panels according to regional exposure and sensitization patterns are increasingly being discussed. Regional sensitization rates according to SPTs based on the most recent GA2LEN baseline series in Central Germany were retrospectively analyzed for 960 consecutive patients with respiratory symptoms at our university outpatient clinic. Additional SPT allergens of interest were further analyzed. High sensitization rates to the baseline SPT series were observed in our highly selected study cohort. The positivity rates were particularly high for olive pollen (30.8%) and plantain pollen (33.4%). Positive olive and birch pollen SPTs were found in 98.5% of olive-ash-birch pollen tested patients. High SPT positivity rates (98.1%) for plane tree and olive tree pollen were found, whereas only six patients (1.9%) were diagnosed with exclusive cypress pollen sensitization. Subgroup analysis of SPTs for palm tree pollen revealed that 92% of patients with palm tree positivity showed polysensitization, and all but one patient had concomitant grass pollen sensitization. Regular evaluations of SPT series may be necessary because of climate change, extract production, and increasing population mobility. Ash and cypress pollen extracts could currently be removed from the baseline SPT panel without significantly decreasing diagnostic accuracy. Positive SPTs to non-native palm tree pollen may indicate the presence of IgE to cross-reacting panallergens, which may help to differentiate primary sensitization from cross-reactivity directly. Limitations include the retrospective monocentric design and lack of molecular IgE confirmation.

Background: European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2020 proposed a novel primary chronic rhinosinusitis (CRS) phenotype classification. As the endotype and phenotype of primary CRS are highly heterogeneous, clinical evaluation to match these endotypes and corresponding clinical biomarkers with these novel phenotypes is still limited. This study aimed to evaluate the correlation between clinical inflammatory biomarkers and primary CRS phenotype. Materials and Methods: A retrospective study of 78 adult patients diagnosed with primary CRS was conducted. Peripheral eosinophil count, serum-specific immunoglobulin E (ssIgE), and primary CRS phenotyping data were collected from the electronic health record database of Dr. Kariadi General Hospital Semarang. The Chi-square test and phi coefficient were used to assess the correlation between variables. Results: Most patients have polysensitization allergen patterns, predominated by house dust mites (Tyrophagus putrescentiae, Dermatophagoides microceras, and Dermatophagoides farinae) and grass pollens (Bermuda grass,mix grass, and Timothy grass). peripheral eosinophil count and ssIgE are significantly correlated to primary CRS phenotype (r=+0.407, p 0.001; r=+0.342, p=0.002; respectively). We also found a small portion of some peculiar conditional probabilities of having non-eCRS given patients have peripheral eosinophilia and positive ssIgE (6.2% and 17.3%, respectively). Conclusion: peripheral eosinophils count and ssIgE are correlate to the CRS phenotype.

Abstract Purpose Allergic rhinitis (AR), which is prevalent among children and adolescents, often impairs quality of life and coexists with asthma. Allergen immunotherapy (AIT), particularly sublingual immunotherapy (SLIT), is recommended for individuals with insufficient response to standard treatments. While adherence is critical to AIT effectiveness, its impact on the use of allergy medications remains unclear. This study aimed to investigate the association between adherence to SLIT for grass pollen and use of prescription allergy medications. Methods A nationwide cohort study was conducted using Danish health registries. Children and adolescents initiating SLIT from 2007–2022 were classified as adherent (≥ 80% of defined daily dose [DDD]) or nonadherent (&lt; 1 year of DDD). Individuals with intermediate adherence were excluded. Primary outcomes were annual use and dosage of prescription oral antihistamines, nasal corticosteroids, and inhaled corticosteroids, analyzed using two-step regression models adjusted for age and sex. Results Among 2500 children and adolescents, 1118 were adherent and 446 nonadherent. Over time, the adherent group showed a significant reduction in antihistamine and nasal corticosteroid use compared to the nonadherent group, relative to pretreatment levels (p &lt; 0.05). No significant difference in inhaled corticosteroid use was observed. Among users, mean annual doses of allergy medications were higher in the adherent group, likely reflecting broader adherence behaviors. Conclusion Adherence to SLIT was associated with reduced use of symptomatic allergy medications, highlighting its clinical importance. Strategies to improve adherence—such as patient education and structured follow-up—may enhance outcomes in pediatric AR management.

Background: Allergen immunotherapy (IT) in Europe is generally administered as monoallergen IT. However, in some patients and in other parts of the world, multiallergen IT is common practice. A key question is whether allergens in a mixture retain their allergenicity over time. Objective: To demonstrate if allergenicity, as measured by skin-prick testing (SPT), is maintained after 6 months in a sublingual immunotherapy (SLIT) maintenance vial with three allergen extracts in a single individual vaccine, including two pollens and Dermatophagoides. Methods: We prepared two maintenance SLIT vials that contained mixed Dermatophagoides species (2000 AU/mL), ash tree and Bermuda grass pollens (1:50 w/v), one 6 months before SPT and the second 0-2 weeks before SPT, and three fresh vials (0-2 weeks before SPT) for each individual allergen. Duplicate SPTs were conducted with all five vials, diluent and positive (histamine 1 mg/mL) controls. Wheals were measured at 10 minutes (controls) and 20 minutes (allergen vaccines). The mean wheal diameter was calculated as the average of the longest and orthogonal diameters, i.e., (D1 + D₂)/2. For each allergen extract, two replicate wheals were obtained per participant; their mean diameters were averaged to yield a patient-level mean wheal diameter. These patient-level means were then averaged across all the participants. The paired t-test was used to calculate statistically significant differences between the mean wheal diameters of the extracts, with significance at p < 0.05. Results: The mean ± standard deviation wheal diameter produced by the 6-month-old and the fresh extracts were 8.7 ± 3.3 mm and 8.4 ± 2.87 mm, respectively. This difference was not significant. Moreover, the potency of both pollen extracts was conserved when mixed with house-dust mite extracts. Conclusion: In our pilot study, allergenicity of tree and grass pollen allergens in an allergen mix with Dermatophagoides in a SLIT maintenance vial was maintained over 6 months. Replication in a larger population would consolidate our findings.

Asthma is a chronic respiratory disease comprising different pheno- and endotypes. Diagnostic tools for the identification of allergic versus non-allergic asthma are needed for new precision medicine-based treatments. To determine IgE sensitization profiles to multiple micro-arrayed allergen molecules in adult patients with asthma in the Austrian LEAD (Lung, hEart, sociAl, boDy) cohort; to compare IgE- and non-IgE sensitized patients with asthma; and to define possible allergen-specific immunotherapy concepts for sensitized patients. Out of 893 patients with a history of asthma, patients with current asthma (n = 436) were analyzed for IgE sensitizations to 110 micro-arrayed molecules from airborne and food allergen sources and by skin prick testing (SPT) with 10 allergen extracts (English plantain, mugwort, ragweed, timothy grass, ash tree, mites, dog, cat, Alternaria alternata, and Fagales mix). Clinical asthma-related parameters were compared between patients with IgE sensitization to asthma allergen molecules and non-IgE sensitized patients with asthma. IgE sensitization was detected in 73.2% of patients with asthma using 63 micro-arrayed respiratory allergens. The most recognized respiratory outdoor allergen molecules were Bet v 1 (32.8%) and Ole e 1 (23.2%) followed by grass pollen, ragweed, and mugwort allergens. Fel d 1 was the most frequently recognized respiratory indoor allergen molecule (42.7%) followed by house dust mite and dog allergen molecules. Micro-arrayed allergens allowed the identification of IgE reactivity profiles indicative of genuine sensitizations to different allergen sources. IgE-sensitized patients were significantly younger than non-IgE-sensitized patients with asthma (median age 44 versus 58 years). Patients sensitized to respiratory allergens showed significantly better lung function (FEV1, FVC and FEV/FVC) and less dyspnea but more allergic bronchitis than non-IgE-sensitized patients with asthma. More IgE-sensitized patients used antihistamines but fewer inhaled corticosteroids than non-IgE-sensitized patients with asthma. Interestingly, eosinophil counts were lower both in ICS-treated as well as untreated sensitized patients than in non-sensitized patients with asthma. Molecular allergy diagnosis allowed the detection of genuine IgE sensitizations in adult patients with asthma; enabling stratification for precision medicine-based forms of personalized treatments such as allergen-based immunotherapy (AIT) and/or administration of biological treatments in asthma.

A Wideband Integrated Bioaerosol Sensor (WIBS) was used in conjunction with chemical tracer analysis for the first time during the 2022–2023 grass pollen season in Melbourne, Australia. WIBS detected continuous levels of bioaerosol throughout the campaign. From 18th November to 7th December 2022, fluorescent particles accounted for an average of 10% of total particles in number, corresponding to an estimated 0.18 μg m−3 PM2.5 (14%) and 0.49 μg m−3 PM10 (25%). Using mannitol as a chemical tracer, fungal spores were estimated to contribute to an average of 2% of PM2.5 and 9% of PM10 mass. Analysis of fructose in PM2.5 as a marker for sub-pollen particles (SPPs) showed elevated concentrations during periods of hot and dry weather. There was negligible fructose observed with rain, suggesting that SPP production is not limited to water absorption processes or high relative humidity in Melbourne. Estimates of SPP mass via fructose corresponded to the equivalent of 1.1 m−3 intact pollen grains on average, 2% of the total pollen concentration, 7% of PM2.5 fluorescent particle mass, and 1% of PM2.5 mass. New hourly measured grass pollen data confirmed the timing and magnitude of grass pollen emissions in the Victorian Grass Pollen Emission Model (VGPEM) and captured the strong diurnal variation. Five grass pollen rupturing mechanisms using different meteorological drivers were tested against the WIBS and fructose measurements. Whilst the WIBS and model were not well correlated, likely due to the complex mixture of bioaerosols and low relative abundance of SPPs, the mechanical wind speed rupturing mechanism represented the fructose time series well. Conceptually, this suggests that mechanical rupturing describes SPP formation during hot and dry conditions in Melbourne. Long-term measurements in Melbourne will improve SPP formation process forecasting.

BackgroundEnvironmental exposure chambers (EECs) provide a controlled and reproducible setting for studying allergic rhinitis, allowing standardized exposure to aeroallergens. However, real-time symptom monitoring remains challenging, particularly as patients must be observed remotely while inside the chamber.ObjectiveThis study aimed to design, implement, and evaluate an integrated eHealth system that leverages digital tools for data collection and real-time clinical monitoring during EEC exposures. The goal was to streamline workflow, enhance data reliability, and improve patient safety during allergen challenges.MethodsWe conducted a prospective pilot study in a validated EEC at Ramón y Cajal University Hospital. A total of 34 provocation tests were conducted: 27 in patients with confirmed grass pollen allergy and 7 in nonallergic controls. All exposures took place outside the pollen season using standardized Phleum pratense (grass pollen) at concentrations of 940±100 grains/m³. Clinical data were collected using REDCap (Research Electronic Data Capture; Vanderbilt University), a secure electronic data capture platform. Surveys were automatically scheduled and included standardized instruments: Visual Analog Scale (VAS), Total Nasal Symptom Score (TNSS), Total Ocular Symptom Score (TOSS), asthma symptom questionnaires, peak expiratory flow (PEF), and peak nasal inspiratory flow (PNIF). Data were visualized in real time using Power BI dashboards (Microsoft Corp).ResultsAmong allergic patients, 85% had a positive response to the allergen exposure, with a median TNSS of 6 (IQR 6‐7), while controls showed no positive reactions. Mean exposure time for positive cases was 48.9 minutes (SD 28.3), as patients were withdrawn early upon reaching symptom thresholds. The REDCap system was configured to collect symptom surveys at 15-minute intervals, allowing up to 6 entries per patient during exposure, depending on clinical tolerance. This setup enabled consistent symptom monitoring and integration with Power BI for real-time visualization. All records were successfully synchronized between REDCap and Power BI. Informal feedback from medical staff highlighted improved workflow and usability.ConclusionsThe integration of REDCap with Power BI enabled automated, real-time tracking of symptoms during EEC exposures. This eHealth solution enhanced clinical oversight, supported timely decision-making, and ensured patient safety. The platform provides a flexible and reproducible model for use in allergen exposure studies and other clinical settings requiring structured remote monitoring. Clinical response data are reported in a separate validation study.

BackgroundAllergic rhinitis (AR) triggered by pollen is a growing global public health concern. This study aimed to: 1) analyze IgE reactivity to grass and weed pollen in Thai AR patients; 2) assess the prevalence and intensity of IgE-reactive protein bands; and 3) investigate cross-reactivity among pollen species.MethodsSera were collected from Thai adult AR patients in Bangkok, Thailand, and skin prick test (SPT) data were obtained. ELISA assessed IgE reactivity to pollen extracts from four grasses (Bermuda grass, para grass, Johnson grass, Manila grass) and two weeds (nutsedge, careless weed) using 119 patient sera. Immunoblot identified IgE-reactive protein bands using 65 patient sera with positive SPT. Cross-reactivity was confirmed by immunoblot and ELISA inhibition assays.ResultsJohnson grass showed the highest ELISA optical density (OD) values. Significant positive correlations (rs = 0.740 to 0.935, p < 0.0001) in IgE reactivity were observed among pollen species, with stronger correlations among grasses. Immunoblot identified 30 kDa and 63 kDa proteins as major IgE-reactive proteins in grasses, and 25 kDa and 75 kDa proteins in nutsedge. Strong positive correlations were found within grass species for number of bands, ELISA OD, and SPT wheal size. A positive correlation existed between ELISA and SPT results (rs = 0.27, p = 0.030). Inhibition assays confirmed cross-reactivity among grass and weed species.ConclusionThis study highlights variability in pollen sensitization, cross-reactivity, and potential novel allergens in Thai AR patients. These findings are crucial for enhancing pollen allergy understanding and improving diagnostic and treatment, particularly in tropical/subtropical regions.

Background: Chronic hepatitis B (CHB) remains being a major public health threat, and currently existing CHB therapies have limited efficacy and side effects. We have recently developed a vaccine termed VVX001 based on a recombinant fusion protein consisting of the preS domain of the large surface protein of hepatitis B virus (HBV) fused to grass pollen allergen peptides. VVX001 has been shown to induce preS-specific antibodies in grass pollen allergic patients, and sera of immunized subjects inhibited HBV infection in vitro. Methods: In this study we investigated if immunization with VVX001 can induce preS-specific antibodies in CHB using the adeno-associated virus (AAV)-HBV murine model of CHB. Six groups of C57BL/6 female mice (n = 6) were transduced with AAV-HBV or AAV-Empty, and after six weeks, they were immunized five times with 20 µg of aluminum hydroxide-adsorbed VVX001 or preS or vehicle (Alum alone). Serum samples were taken continuously. Two weeks after the last immunization, spleen and liver mononuclear cells were collected. Serum reactivity to preS and preS-derived peptides was assessed by ELISA. B-cell responses were measured by ELISPOT assay, and intrahepatic lymphocyte (ILH) counts were determined by FACS. HBV DNA, HBsAg, HBeAg, ALT, and AST were assessed using commercial kits. Results: Our results show that VVX001 induces preS-specific IgG antibodies that cross-react with different HBV genotypes A-H and are directed against the sodium taurocholate co-transporting polypeptide (NTCP) receptor binding site of preS both in mice with and without HBV. Actively immunized AAV-HBV-treated mice had a higher number of intrahepatic lymphocytes than vehicle-vaccinated and mock-transduced animals. Conclusions: These findings encourage performing further trials to study the potential of VVX001 for therapeutic vaccination against CHB.

Abstract Grass pollen constitutes a significant public health concern in Australia, particularly for individuals with seasonal allergic rhinitis and asthma, due to its strong association with epidemic thunderstorm asthma (ETSA) events, which are getting more frequent due to climate change. The combined effects of humidity and lightning during ETSA events cause intact grass pollen to rupture and release small particles that can trigger severe asthma attacks, leading to increased hospital admissions. To help prevent this, researchers began collecting and monitoring local pollen data that contribute to ETSA warning systems. In Australia, expert pollen counters rely on Hirst-type traps, but these machines take 24 h to operate. Some modern machines have been designed to monitor pollen faster, but they are not able to determine the state of the pollen (i.e., intact or ruptured). The advent of artificial intelligence (AI) presents an opportunity to enhance pollen monitoring by accurately identifying not only pollen taxa but also the state of the pollen. Using AI to monitor ruptured pollen could improve the accuracy and efficiency of warning systems, thereby helping to prevent the severe outcomes associated with ETSA events.

ABSTRACTBackgroundRegulatory authorities recommend a combination of symptom and medication scores during the grass pollen season as a primary endpoint for Phase III allergen immunotherapy (AIT) trials targeting allergic rhinoconjunctivitis. However, many composite primary endpoint scales exist; none are validated, nor do they have a well‐justified minimal clinically important difference (MCID).MethodsDirect patient feedback from 1071 grass‐allergic patients was obtained to determine the minimally relevant improvement in allergic symptoms and translated into an MCID for the EAACI recommended CSMS0–6. Additionally, a clinically relevant threshold for the validated Rhinitis Quality of Life Questionnaire (RQLQ(S)) was determined from studies of registered SLIT products and subsequently used as an anchor to derive the MCID for CSMS0–6 using the data of a Phase III clinical trial with PQ Grass 27,600 SU (RESONATE).Results69% of grass‐allergic patients were satisfied with a 1‐point‐improvement (e.g., from “severe” to “moderate”) in their most severe symptom. This translated into an MCID range for CSMS0–6 of −0.23 to −0.21 points or −17% to −16%. Furthermore, a −0.34 point difference in RQLQ(S) compared to placebo was justified as clinically meaningful based on Phase III data from 2 registered SLIT grass tablets. Using this RQLQ(S) threshold as an anchor, an MCID of CSMS0–6 of −0.21 points (−16%) was derived using RESONATE.ConclusionsBoth patient feedback and RESONATE results support an average MCID of −0.22 points on the CSMS0–6 scale and −16% on a composite primary endpoint scale, providing minimal thresholds to be achieved after AIT compared to placebo to conclude a positive Phase III trial outcome.