Chronic rhinosinusitis (CRS) is a common, heterogeneous upper airway inflammatory disorder, affecting approximately 12% of the general population. The disease is clinically stratified into CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP), including the most severe subtype of non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD). In order to identify molecular signatures and biomarkers allowing for the distinction between different disease endotypes and controls, we employed targeted proteomics combined with bioinformatics and Machine Learning analyses. Nasal secretions and serum from 80 patients (20 each of CRSsNP, CRSwNP, N-ERD, and disease controls) were subjected to high-throughput targeted proteomics (Olink®) and the expression patterns of 161 and 2677 proteins, for nasal secretions and serum, respectively, analyzed alongside clinical evaluations of nasal polyp and smell test scores. Two distinct expression patterns were identified in nasal secretions: proteins associated with macrophage recruitment and type 2 inflammation were increased in CRSwNP and N-ERD, whilst proteins associated with innate immunity, particularly Toll-like receptor 4 signaling (TLR4), were gradually downregulated from DC to N-ERD. Furthermore, using Machine Learning, we confirmed two potential biomarkers for nasal polyposis: the glial cell line-derived neurotrophic factor (GDNF) in nasal secretions and Charcot-Leyden crystal protein (CLC) in serum. Our findings provide unique insights into CRS pathophysiology and highlight potential biomarkers for precision diagnosis and treatment, particularly in severe cases such as N-ERD. Our findings enhance the understanding of CRS pathophysiology and identify potential biomarkers for precise diagnosis, especially in severe cases like N-ERD, informing the design of targeted therapeutic strategies.

The balanced activity of the cytoprotective transcription factor NRF2 is central for maintaining redox, metabolic-energetics, and proteome homeostasis, as well as for regulating inflammatory responses, among other functions. Activated NRF2 regulates the expression of hundreds of genes containing antioxidant response elements (AREs) or electrophile response elements (EpRE) in their regulatory regions, often promoting cytoprotection under stress conditions and contributing to defence against various pathologies and non-communicable diseases (NCDs). The products of increased NRF2 activity, detected systemically, may originate from either the white blood cells, the cells of the vasculature or tissue-derived products that could be secreted into biological fluids. Therefore, assessing basal and inducible NRF2 activity in blood or other biofluids is crucial for inferring NRF2 responses in local and often inaccessible tissues. In previous work, we identified a panel of six biomarkers - Glutamate-cysteine ligase catalytic subunit (GCLC), Glutamate-cysteine ligase modifier subunit (GCLM), Haem oxygenase 1 (HMOX1), NAD(P)H quinone dehydrogenase 1 (NQO1), Sulfiredoxin 1 (SRXN1), and Thioredoxin reductase 1 (TXNRD1) - as indicators of NRF2 activity. In the current study, we assess their utility in a clinical setting to measure NRF2 activation in a disease context. Here we discuss findings on how NRF2 activity in accessible human samples can reveal its involvement in various NCDs and its connection to clinical aspects such as diagnosis, disease progression and response to therapy.

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.

Over the past century, research on vitamin E has evolved from its initial identification as a fertility factor to the recognition of α-tocopherol (α-TOH) as an essential micronutrient with antioxidant and gene regulatory functions. Despite extensive investigation, controversies persist regarding its precise biological role, clinical efficacy, and classification as a vitamin. This review summarizes scientific milestones in vitamin E (tocochromanol) research. It highlights recent advances in understanding the absorption, metabolism, and molecular mechanisms of vitamin E. The review also outlines unresolved questions and methodological challenges. The focus is on α-TOH and its metabolites, which exhibit biological activities beyond classical antioxidant effects, such as the regulation of inflammation, lipid metabolism, and immune responses. Evidence from genetic, biochemical, and clinical studies supports the essentiality of α-TOH in humans, as demonstrated by ataxia with vitamin E deficiency (AVED). Other tocochromanols and their metabolites exhibit promising biological activities that suggest potential therapeutic applications. However, their physiological relevance must be confirmed. Advances in metabolomic profiling and molecular modeling now allow for a more comprehensive characterization of vitamin E metabolism and function. Understanding the molecular pathways and biological roles of vitamin E and its derivatives is crucial for refining its definition, establishing evidence-based dietary recommendations, and evaluating its potential in disease prevention and therapy.

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)