Safety of 300IR house dust mite sublingual tablet from pooled clinical trial and post-marketing data.

Background: The 300IR house dust mite (HDM) sublingual immunotherapy (SLIT) tablet is approved for treatment of HDM-induced allergic rhinitis (AR). To provide a comprehensive review of the 300IR HDM-SLIT tablet safety profile based on randomized controlled trial (RCT) pooled data and post-marketing (PM) pharmacovigilance data. Methods: Subjects (5-65 years) with confirmed HDM-AR with or without controlled asthma were treated with 300IR or placebo in 8 RCTs. Reported treatment-emergent adverse events (TEAEs) were pooled and analyzed descriptively in subsets of adults/adolescents and children. Adverse reactions (ADRs) collected from spontaneous reporting and PM studies through a pharmacovigilance system since the first marketing authorization were also analyzed. Results: Across RCTs, 1853 subjects were treated with the 300IR HDM-SLIT tablet and 1846 with placebo. In both subsets of adults/adolescents and children whichever their asthma status, treatment-related TEAEs of higher incidence in active groups vs placebo were mostly consistent with mild or moderate local application-site reactions. They were mainly reported on the first days of treatment and decreased over time. 4 severe laryngopharyngeal reactions (2 requiring adrenaline/epinephrine) and 1 moderate eczema considered serious rapidly resolved with medications; no anaphylaxis was reported. In PM settings, ADRs reported in more than 235,000 patients were in line with RCT findings. Severe systemic reactions occurred rarely; 12 anaphylactic reactions resolved safely (5 with adrenaline). No new safety signal was raised. Conclusion: Safety data from RCTs and more than 7 years of real-life experience confirmed the favorable safety profile of 300IR HDM-SLIT tablet in patients across different regions, regardless of age and asthma status. Clinical trial registrations: NCT00674700; Retrospectively registered 06 May 2008.NCT01199133; Retrospectively registered 09 September 2010.NCT01527188; Retrospectively registered 01 February 2012.NCT02443805; Registered 29 April 2015/EudraCT 2014-004223-46; Registered 16 September 2015.jRCT2080221872/JapicCTI-121917; Registered 01 August 2012.jRCT2080222929/JapicCTI-15298; Registered 04 August 2015.

Disease modification in chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) is a debilitating, inflammatory skin condition characterized by infiltrating immune cells. Available treatments are limited to improving the signs and symptoms. There is an unmet need to develop therapies that target disease-driving pathways upstream of mast cell activation to inhibit or delay the progression of CSU and associated comorbidities. Here, we aim to define disease modification due to a treatment intervention and criteria that disease-modifying treatments (DMTs) must meet in CSU. We have defined disease modification in CSU as a favorable treatment-induced change in the underlying pathophysiology and, therefore, the disease course, which is clinically beneficial and enduring. A DMT must fulfil the following criteria: (1) prevents or delays the progression of CSU, (2) induces long-term, therapy-free clinical remission, which is the sustained absence of CSU signs and symptoms without the need for treatment, and (3) affects the underlying mechanism of CSU, as demonstrated by an effect on disease-driving signals and/or a biomarker. DMTs in CSU should slow disease progression, achieve long-lasting disease remission, target disease-driving mechanisms, reduce mast cell-activating IgE autoantibodies, target cytokine profile polarization, and normalize the gut microbiome and barrier. Treating CSU at the immune system level could provide valuable alternatives to pharmacotherapy in CSU management. Specific DMTs in CSU are yet to be developed, but some show potential benefits, such as inhibitors of Bruton's Tyrosine Kinase, IL-4 and IL-13. Future therapies could prevent CSU signs and symptoms, achieve long-term clinical benefits after discontinuing treatment, and prevent associated concomitant disorders.

Biologics Reduce Symptoms of Alcohol Intolerance Better than Aspirin Desensitization in Patients with N-ERD and Nasal Polyps.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) exacerbated respiratory disease (N-ERD) is associated with chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and NSAID hypersensitivity. An overproduction of leukotrienes characterizes the pathomechanism of the disease. N-ERD patients often report breathing difficulties after consuming alcohol. These symptoms have been observed in patients receiving either aspirin therapy after desensitization (ATAD), therapy with the biologics dupilumab (anti-IL-4Ra antibody) and omalizumab (anti-IgE antibody), or intranasal corticosteroid treatment (INCS). METHODS: This retrospective, real-world study assessed the severity of alcohol-related and non-alcohol-related respiratory symptoms in CRSwNP/N-ERD patients 3-6 months after ATAD, biologic (dupilumab or omalizumab), or INCS therapy. A total of 171 patients (98 women and 73 men) were enrolled in the study. All groups received standard INCS therapy. Sixty-three patients were treated with ATAD; 48 received biologics (dupilumab n = 31; omalizumab n = 17); and 60 received INCS only and served as a control group. Alcohol-dependent symptoms and typical CRS symptoms (alcohol-independent) were quantified using visual analog scales (VAS). RESULTS: ATAD and biological therapy significantly reduced VAS scores for alcohol dependence and CRS symptoms. In the control group receiving INCS, only non-alcohol dependent CRS symptoms improved significantly (p < 0.05). The most significant differences in pre/post scores were observed in patients receiving dupilumab, with the most significant improvement in alcohol-dependent and CRS symptoms (dupilumab > omalizumab > ATAD). CONCLUSIONS: This real-world study shows that alcohol-related respiratory symptoms are a relevant parameter in CRSwNP/N-ERD patients. Patients benefit more from biologic therapy than from ATAD in terms of their alcohol-related symptoms and other CRS symptoms. Future studies should include placebo-controlled oral alcohol challenge.

AWMF mold guideline "Medical clinical diagnostics for indoor mold exposure" - Update 2023 AWMF Register No. 161/001.

None.

Digitally-enabled, person-centred care (PCC) in allergen immunotherapy: An ARIA-EAACI Position Paper.

In rhinitis and asthma, several mHealth apps have been developed but only a few have been validated. However, these apps have a high potential for improving person-centred care (PCC), especially in allergen immunotherapy (AIT). They can provide support in AIT initiation by selecting the appropriate patient and allergen shared decision-making. They can also help in (i) the evaluation of (early) efficacy, (ii) early and late stopping rules and (iii) the evaluation of (carried-over) efficacy after cessation of the treatment course. Future perspectives have been formulated in the first report of a joint task force (TF)-Allergic Rhinitis and Its Impact on Asthma (ARIA) and the European Academy of Allergy and Clinical Immunology (EAACI)-on digital biomarkers. The TF on AIT now aims to (i) outline the potential of the clinical applications of mHealth solutions, (ii) express their current limitations, (iii) make proposals regarding further developments for both clinical practice and scientific purpose and (iv) suggest which of the tools might best comply with the purpose of digitally-enabled PCC in AIT.

An emerging aeroallergen in Europe: Tree-of-Heaven (Ailanthus altissima [Mill.] Swingle) inventory and pollen concentrations - Taking a metropolitan region in Germany as an example.

Urban areas are often hotspots for the dissemination of non-native (invasive) plant species, some of which release (potentially) allergenic pollen. Given the high population density in cities, a considerable number of people can be regularly and potentially intensively exposed to the pollen from these plants. This study delves into the Tree-of-Heaven (Ailanthus altissima, [Mill.] Swingle), native to East Asia, which is known for its high invasiveness in temperate regions worldwide, particularly favoring urban colonization. This study explores the botanical and aerobiological dimensions of this species using the central European metropolitan region of Berlin, Germany, as a case study, and provides a comprehensive global overview of allergological insights. The number of Ailanthus trees decreased markedly from the center to the periphery of Berlin City, following a temperature gradient. The same spatial trend was mirrored by airborne Ailanthus pollen concentrations measured with volumetric spore traps (Hirst-type) at five sites using seven traps. Ailanthus pollen was most abundant around midday and in the afternoon, with concentrations tenfold higher at street level than at roof level. The Ailanthus flowering period in June and July coincided well with the pollen season. To the best of our knowledge this is the first study to investigate Ailanthus altissima pollen production. On average, 5539 pollen grains were found per anther. A literature review on the allergy relevance of Ailanthus altissima pollen indicates the high allergenic potential of pollen from this species. Considering the anticipated expansion of suitable habitats for Ailanthus owing to global warming and the allergological significance of its pollen, it is recommended to include Ailanthus pollen in routine pollen monitoring, particularly in areas colonized by this species. This comprehensive study provides new insights into a pollen taxon whose significance as an emerging aeroallergen should be factored into plant selection and greenspace management in all temperate regions.

Individual wearable air purifier protects against pollen, house dust mite, and cat allergens: Report from an allergen exposure chamber.

PURPOSE: Evaluation of a new individual wearable air purifier (Respiray Wear A+) for birch pollen, house dust mite (HDM), and cat-allergic rhinoconjunctivitis (ARC) patients in a standardized allergen exposure chamber (AEC). MATERIALS AND METHODS: Eligible allergic patients were exposed to birch pollen, HDM raw material, and cat allergen in an AEC for 60 minutes without (V1) and with (V3) the use of the Respiray device. Nasal, ocular, bronchial, and other symptoms were rated by the patients every 10 minutes, and their wellbeing, peak nasal inspiratory flow (PNIF), and lung function parameters were assessed every 30 minutes. The primary endpoint was the change in the median of the total symptom score (TSS) at V3 compared to V1 at 60 minutes of exposure. The secondary endpoints consisted of the total nasal symptom score (TNSS) and total eye symptom score (TESS). RESULTS: 23 patients with birch pollen allergy, 37 patients with HDM allergy, and 41 patients with cat allergy were included in the analysis. Significant reduced symptom scores of ~ 49% were observed when using Respiray Wea A+ under birch pollen exposure (p < 0.05) in the primary endpoint TSS (V3 2.43 compared to V1 4.78). An 48% reduction of symptoms was seen in TSS in case of HDM exposure (V3 3.59; V1 6.92, (t-test: p < 0.01)) and the highest reduction of TSS (60%) under Respiray A+ using cat allergens (V3 2.95, V1 7.44, (t-test p < 0.01) after 60 minutes of exposure. The personal wellbeing revealed clinically meaningful improvements over time in all three studies which manifested in a lower symptom increase during the final allergen exposures. CONCLUSION: The individual wearable air purifier Respiray Wear A+ protects significantly against airborne pollen, HDM, and cat allergens and may be a very useful device for avoiding indoor allergens in a new way.

Efficacy of 300 IR house dust mite immunotherapy as a function of disease activity: Tertile analysis in clinical trials.

BACKGROUND: The symptoms of house dust mite (HDM)-induced allergic rhinitis (AR) vary with changes in exposure related to the weather or the domestic environment. In allergen immunotherapy (AIT) studies, a certain level of AR disease activity is necessary to demonstrate treatment efficacy; the latter can be underestimated if a substantial proportion of the patient population is weakly symptomatic. OBJECTIVE: To better estimate the real treatment effect of a HDM sublingual AIT (SLIT) tablet, we analysed the results of natural field studies in detail by applying a tertile approach. METHODS: We used data from three randomised, controlled trials (RCT) in a total of 2585 patients with AR treated with the 300 index of reactivity (IR) HDM SLIT-tablet or placebo. The study centres were grouped into tertiles according to the level of combined symptom and medication scores in patients in the placebo group. In each tertile, the difference between SLIT and placebo was assessed through an analysis of covariance. RESULTS: In the three RCTs, combined scores were found to be similar in the SLIT and placebo groups in the low tertiles. The treatment effect of the 300 IR HDM tablet increased in the medium and high tertiles, with notably significant differences versus placebo in the highest tertile and greater (ranging from -21% to -39%) than in the entire study population (-13% to -20%). The positive relationship between treatment efficacy and the combined score in each tertile was independent of the RCT and the score used. CONCLUSION AND CLINICAL RELEVANCE: Application of the tertile approach to AIT studies in a field in which many variables interact strongly might provide more accurate and meaningful measurements of efficacy and benefit for patients, better reflecting their real-life condition.