Christina Morgenstern

Background: In allergic rhinitis (AR), effector cell activation via allergen‐specific (s) IgE cross‐linking is well established, yet the in vivo kinetics of allergen‐specific antibody responses and their modulation of effector cell reactivity after nasal allergen exposure warrant further investigation. We therefore set out to characterize the sequence and timing of systemic and local antibody responses and basophil/mast cell sensitivity after nasal allergen challenge, and their influence on subsequent seasonal responses. Methods: In this randomized, double‐blind, placebo‐controlled trial, birch pollen–allergic adults received three daily nasal challenges with birch pollen extract ( n = 20) or placebo ( n = 10) in autumn. sIgE, sIgG, sIgG1, sIgG4 and sIgA levels, basophil activation (BAT), and titrated skin prick test (tSPT) responses were measured biweekly in nasal mucosal lining fluid (nMLF), blood and skin for 3 months, and before, during, and after seasonal exposure. Results: Allergen but not placebo challenge induced sequential sIgE rises, first in serum, then nMLF, mirrored by sIgG responses. Basophil sensitivity peaked with serum sIgE at 4 weeks, followed by maximal mast cell sensitivity in tSPT at 8 weeks. Allergen‐specific antibodies remained elevated through the pre‐seasonal and seasonal periods. Allergen‐challenged subjects showed reduced sIgE rise and lower effector cell sensitivity during the following pollen season. Conclusion: Out‐of‐season high‐dose nasal allergen exposure enhances sIgE levels and effector cell sensitivity as well as sIgG and nasal sIgA responses. The latter appear to later attenuate seasonal amplification of allergic responses. Trial Registration: ClinicalTrials.gov ID: NCT03644680

Ailanthus altissima (tree of heaven) is among the most abundant and widespread neophytic plants in Austria. The pollen season of Ailanthus usually ranges from the beginning of June until the mid of July, showing one peak period around the mid of June in Vienna (Austria). Over a span of 48 years (1976–2023), pollen data of Ailanthus was gathered from aerobiological samples and assessed for a temporal trend. In addition, weather data from Vienna (temperature, precipitation, relative humidity and sun hours) was incorporated to find possible associations with Ailanthus pollen indices. The change in the pollen season for Ailanthus described in this study has already manifested and is ongoing. Temperature and sunshine hours have a direct impact on the flowering of urban trees, indicating that global climate change may be a major driver towards more intense pollen and allergy seasons.

Background: Non‐steroidal anti‐inflammatory drug‐exacerbated respiratory disease (N‐ERD) is characterised by the clinical triad of hypersensitivity to NSAIDs, nasal polyposis, and asthma. The cells and mediators causing acute symptoms when driving the hypersensitivity reaction to acetylsalicylic acid (ASA) ingestion, remain poorly defined. Objective: To investigate the dynamics of nasal mediators during ASA provocation in N‐ERD patients before and 24 weeks after therapy with the IL‐4 receptor alpha‐blocking antibody dupilumab (EudraCT (2019‐004889‐18) and ClinicalTrials.gov (NCT04442256)). Methods: Nasal mucosal lining fluids of patients with N‐ERD, chronic rhinosinusitis patients with nasal polyp (CRSwNP) and healthy disease controls were collected at selected time points up to 2 h after ASA provocation. Analysis of thirty‐three different inflammatory mediators as well as transcriptomic profiling was performed. In N‐ERD patients, provocation was repeated after 24 weeks of dupilumab therapy. Results: Sixty minutes after provocation with ASA, N‐ERD patients showed a significant increase in type 2 associated cytokines (i.e., TSLP, IL‐5 and eotaxin‐3) as compared to the other patient groups. This effect was diminished after 24 weeks of dupilumab therapy and was independent of the development of ASA tolerance. Transcriptomics revealed dampened upregulation of type 2 associated pathway genes (i.e., AREG ) as well as enhanced downregulation of lipid (i.e., ALOX15 ) and peroxisome metabolisms (i.e., NOS2 ) at ASA provocation after dupilumab therapy. Conclusion and Clinical Relevance: Treatment with dupilumab leads to reduced nasal type 2 cytokine secretion and distinct changes in transcriptomic profile during ASA provocation, but changes in type 2 mediators show no association with tolerance development. Trial Registration: EudraCT (2019‐004889‐18) and ClinicalTrials.gov (NCT04442256)

The Artemisia (mugwort) pollen season usually ranges from July until September, with one peak period around mid-August in Vienna (Austria). During the last decade, Artemisia pollen was also recorded later in September. This pattern was concluded by a significant peak pollen concentration day in autumn of 2023, which exceeded the usual summer peak pollen concentration day. The Artemisia pollen data from Vienna for the last ten years (2014–2023) were therefore analysed for a temporal trend. In addition, weather data from Vienna (temperature, precipitation, and relative humidity and sun hours) were retrieved and analysed to find a possible association with Artemisia pollen indices. No significant trend could be observed regarding the Artemisia pollen season parameters and no correlation was found between the weather data and the Artemisia pollen integrals during summertime. However, a significant positive correlation was found between higher temperatures during autumn and the occurrence of Artemisia pollen during this time. This suggests that a significant change in the Artemisia pollen season can be expected during years with a mild, summer-like autumn. Until now, it is not clear which species of Artemisia cause the pollination in autumn. A. annua and A. verlotiorum are two major suspects that could have established themselves in Vienna, but further evidence is needed. Considering the impact of global climate change, the shift in the pollen season for Artemisia described in this study could represent a point of no return.

Rationale: Non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is characterized by the clinical triad of hypersensitivity to NSAIDs, nasal polyposis, and asthma. The cells and mediators causing acute symptoms when driving the hypersensitivity reaction to acetylsalicylic acid (ASA) ingestion, remain poorly defined. Objectives: To investigate the dynamics of nasal mediators during ASA provocation in N-ERD patients before and twenty-four weeks after therapy with the IL-4 receptor alpha-blocking antibody dupilumab. Methods: Nasal mucosal lining fluids of patients with N-ERD, chronic rhinosinusitis patients with nasal polyp (CRSwNP) and healthy disease controls were collected at selected time points up to two hours after ASA provocation. Analysis of thirty-three different inflammatory mediators as well as transcriptomic profiling was performed. In N-ERD patients, provocation was repeated after twenty-four weeks of dupilumab therapy. Measurements and Main Results: Sixty minutes after provocation with ASA, N-ERD patients showed a significant increase in type 2 associated cytokines (i.e., TSLP, IL-5, and eotaxin-3) as compared to the other patient groups. This effect was diminished after twenty-four weeks of dupilumab therapy and was independent of the development of ASA tolerance. Transcriptomics revealed dampened upregulation of type 2 associated pathways genes (i.e., AREG ) as well as enhanced downregulation of lipid (i.e., ALOX15 ) and peroxisome metabolisms (i.e., NOS2 ) at ASA provocation after dupilumab therapy. Conclusions: Treatment with dupilumab leads to reduced nasal type 2 cytokine secretion and distinct changes in transcriptomic profile during ASA provocation, but changes in type 2 mediators show no association with tolerance development.