Climate change is causing the spread of common ragweed across Europe, along with rising ground-level ozone (O3) in semi-urban and rural environments. Although elevated O3 has been shown to affect pollen-intrinsic allergenic compounds, here we addressed the lack of in vivo evidence on how ozone-exposed ragweed pollen modulates allergic responses. Ragweed plants were grown in controlled plant growth chambers under control (40 ppb) or elevated (80 ppb and 120 ppb) O3 levels. Aqueous pollen extracts (RWE) from control- or O3-exposed plants were administered in vivo in a murine model for allergic airway inflammation (AAI) and employed in a human in vitro system of monocyte-derived dendritic cells (DCs), key initiators of the allergic response. Adjuvant factors and metabolites in control- and O3-RWE were investigated using ELISA and untargeted metabolomics. Compared to control-RWE, 80 ppb O3 induced a statistically significant enhancement of few AAI parameters, whereas 120 ppb O3 yielded statistically significant dampening effects on AAI. On the same line, in human DCs isolated from atopic donors, RWE O3 80 ppb slightly increased, while RWE O3 120 ppb decreased the expression of maturation markers. Metabolomic profiling revealed pronounced, dose-dependent shifts in pollen primary and secondary metabolites, with moderate stimulation of pro-inflammatory lipid- and protein-derived mediators at 80 ppb, whereas higher O3 levels (120 ppb) induced metabolic degradation resulting in reduced lipid and protein pro-allergenic compounds. Overall, ozone altered ragweed pollen allergenicity in a dose-dependent manner through plant physiological responses to oxidative stress, highlighting the interaction between air pollution and plant physiology in shaping pollen allergenicity in a changing climate.

Background Various mouse models are used to study pollen allergies, but a systematic experimental comparisvon is lacking. We aimed to establish a physiologically relevant adjuvant-free birch pollen allergy model to understand the dynamics of the allergic immune response and to compare the sensitising potential of different self-collected birch pollen extracts in different distinct in vivo and in vitro routes and models. Methods Different intranasal (i. n.) models in BALB/c mice and IL-4 reporter mice (BALB/c:4Get), an intradermal (i. d.) model (BALB/c:4Get), and human dendritic cells (moDCs) were used to investigate the sensitising and inflammatory effects of birch pollen extracts (BPE). A timeseries experiment was performed in the i. n. model to determine the onset of Th2 responses. Bronchioalveolar lavage fluid (BALF), lungs, draining lymph nodes, and serum were analysed for cell infiltrate, cytokines, and antibodies. Results Repeated i. n. instillations of adjuvant-free BPE prepared from commercial pollen resulted in BALF Th2 cells, eosinophilic lung inflammation, and specific serum immunoglobulins in BALB/c mice. After 6 i. n. instillations, eosinophils and CD4+ T cells peaked in BALF, and CD4+IL-4+ and CD4+IL4Rα+ cells peaked in mediastinal lymph nodes. Both, i. n. and i. d. models detected subtle differences in the sensitising potential of BPEs from two self-collected pollen samples. MoDCs showed higher IL-10 release towards the less inflammatory extract. Conclusions Adjuvant-free murine sensitisation models, including intranasal and intradermal routes, as well as a human DC model, covered different aspects of the sensitisation route and temporal resolution. The models may be broadly helpful in screening approaches in studying mechanisms of pollen allergy.

BACKGROUND:Food allergy (FA) arises from a complex interplay between an individual's genetic predisposition and environmental factors, and its prevalence is increasing. Genome-wide association studies to date have been hindered by small sample sizes and varying FA definitions. OBJECTIVE:We sought to identify novel FA risk loci by conducting a genome-wide association study meta-analysis in children and adults by using a multiphenotype approach to ensure a good trade-off between sufficient sample size and valid FA definitions. METHODS:Analyses were conducted separately in children and adults on the basis of the following FA phenotypes: self-report, doctor diagnosis, food-specific sensitization, and doctor diagnosis plus food-specific sensitization. A meta-analysis was performed of genome-wide association studies from up to 16 cohorts of people of European ancestry including 229,426 adults and 14,234 children. Models were adjusted for sex, age, principal components, and, if applicable, further study-specific confounders. Sensitivity models were additionally adjusted for hay fever. Replication was conducted in additional external cohorts and a validation in oral food challenge-defined FA cases. RESULTS:Thirty-seven single nucleotide polymorphisms met suggestive significance (P < 1 × 10-6), with two reaching genome-wide significance: rs116936231 (FGL1) in adult doctor-diagnosed FA plus food-specific sensitization phenotype (stable after additional hay fever adjustment) and rs8022829 (AKAP6-NPAS3), which was significant only in the hay fever-adjusted model in adults. However, neither variant was validated. Further, we identified 3 single nucleotide polymorphisms previously reported for FA and atopic disease. CONCLUSION:This study identified 37 single nucleotide polymorphisms suggestively associated with FA and demonstrated genetic differences across phenotypes. It highlights the need for a unified FA definition and sheds light on FA's shared genetic architecture with allergies.

Developed using the GRADE methodology, these EAACI guidelines provide evidence-based recommendations on the effectiveness of pollen reduction/avoidance strategies for allergic rhinitis (AR) and asthma, the utility of biomarkers for monitoring pollen-induced asthma and the efficiency of mitigation measures and of public health strategies. Systematic and narrative reviews and health economic analysis support the recommendations. According to GRADE, the certainty of evidence was moderate to very low, therefore conditional recommendations are provided to guide healthcare professionals, patients, and policymakers in developing personalized, preventive, and scalable interventions. Reducing/avoiding exposure to pollen should be recommended to reduce the risk of severe asthma exacerbations. Lung function decrease and exhaled nitric oxide increase may be predictive for pollen-induced asthma exacerbations. Real-time pollen monitoring and pollen concentration-based forecast may be recommended for managing pollen-induced AR and/or asthma. Pollutant information should be included in pollen information systems. Combined forecast (weather, pollen, pollutants) and warning systems might reduce the impact of thunderstorm asthma (TA). Emergency department/asthma-related services should be strengthened during pollen season and in TA. Personalized frameworks covering the types and allergenic potential of pollen, the coaggressors and the vulnerability of each patient are needed in daily practice. The fundamental role of prevention should be further prioritized.

BACKGROUND:During the grass flowering season, fungal spores are abundant in outdoor air. We tested for co-sensitisations to grass pollen and fungal spores, assessed the degree of co-exposure, and studied its impact on the nasal mycobiome and immune responses. METHODS:Fungi-specific IgE-levels were studied in 277 individuals with and without grass pollen sensitisation. In a small cohort (n = 7), exposure to grass pollen and fungal spores was monitored during 5 consecutive indoor and outdoor stays in a flowering meadow and correlated with changes in the nasal mycobiome. Cytokines of nasal epithelial cells were studied under stimulation with recombinant grass pollen allergens, with and without fungal spores derived from outdoor isolates. RESULTS:IgE-sensitisation against the studied fungi was significantly more frequent among individuals with grass pollen sensitisation than among those without grass pollen sensitisation. Outdoor exposure resulted in changes in the nasal mycobiome, with a transitory enrichment of environmental fungi, for example, Cladosporium species. Most of the fungi cultivated from outdoor air samples belonged to the genera Fusarium, Cladosporium and Penicillium. Apical co-stimulation of nasal epithelial cells with grass pollen allergens and Fusarium, Cladosporium or Penicillium spores led to an increased loss of transepithelial electrical resistance and induction of pro-inflammatory cytokine release compared to mono-stimulation. CONCLUSION:Frequent co-exposure to fungal spores and grass pollen may increase the chance of acquiring a co-sensitisation to both allergens. Environmental fungi interact with and transitorily change the local mycobiome. Under co-exposure, fungal spores induce nasal inflammation and foster immune responses to otherwise poorly immunogenic pollen allergens.

Precise airborne pollen forecasting is essential for mitigating exposure risks in individuals with pollen-related respiratory diseases such as allergic rhinitis and asthma and for supporting timely public health warning. Moreover, long-term accurate pollen forecasts could also support biodiversity conservation, ecosystem functions, and public-health protection. We developed an ensemble forecasting model for airborne grass (Poaceae) pollen concentrations in three climatically distinct European cities: Augsburg (Germany, transitional temperate-continental), Córdoba (Spain, dry Mediterranean), and Thessaloniki (Greece, humid Mediterranean). Pollen data (2018-2024) from Hirst-type volumetric traps were combined with meteorological parameters (temperature, humidity, precipitation). The 2024 pollen data were used for validation. Of 61 candidates, seven representative model families (Regularized Linear Regression, Extreme Gradient Boosting, Neural Network Autoregression [NNETAR], Random Forest, Support Vector Regression, Prophet-XGBoost hybrid, and Autoregressive Integrated Moving Average [ARIMA]) were selected for the ensemble. Model weights were assigned according to predictive performance. The ensemble achieved R2 values of 0.66 in Augsburg, 0.62 in Córdoba and 0.84 in Thessaloniki, with NNETAR and/or ARIMA contributing most strongly during the pollen season. Lagged pollen concentrations and previous-day temperature emerged as key predictors. When incorporating data from an automatic pollen monitor (BAA500, Helmut Hund GmbH) in Augsburg, the model achieved higher predictive performance (R2 = 0.89). Our findings demonstrate that ensemble-based pollen forecasting may generalize across contrasting bioclimatic regions, while remaining sensitive to local ecological and climatic controls. This framework provides a foundation for more powerful (real-time) forecasting systems aimed primarily at improving daily allergy risk management, while potentially offering complementary insights into longer-term vegetation dynamics under climate variability.

The causative agents of respiratory allergies are bioaerosols, such as house dust mite feces, pollen grains, and fungal spores. Climate change and urbanization are considered to lead to an increase in the load of allergenic bioaerosols due to impacts on plant phenophases and allergenicity. Continuous and efficient monitoring of the atmospheric composition worldwide is essential, given the major changes involved and their impact on climate change. The complexity of the exposome, evolving from single to multiple complex exposures, is explored in this work. Acquiring information from interdisciplinary scientific disciplines, such as aerobiology (for airborne particles of biological origin), aerosol science (for airborne particles of chemical or inorganic material), and integrating this with the actual reactome of patients with respiratory diseases, we aim to provide evidence of the multifactorial nature of this interaction in real life. The objective of this review is to present how we can monitor aerosols and mostly monitor the exposome, especially the biological one, i.e., pollen and fungal spores, and what their impact is, or could be, on respiratory allergies. A huge technological advancement has been required, as traditional methods of particle collection and identification have been based on tedious laboratory procedures, with delays of more than a week. This has limited their practical use to allergic patients and their treating physicians. Automation, real-time high temporal resolution, and the use of artificial intelligence are being increasingly used in medicine. Likewise, this overview summarizes the current aerosol measurement and modeling capabilities and discusses the classification of various aerosol particles and their impact on respiratory allergies. Satellite remote sensing is highlighted as a solution to the gaps in global aerosol representation by examining aerosol load in the atmospheric column in major cities worldwide. We also discuss potential novel threats, such as pioneer bioaerosols and the respiratory epithelial barrier, as well as future insights into the impact of climate change on allergy and asthma. We conclude with a discussion of emerging co-exposures and co-diseases resulting from the ongoing climate change.

With the rising global burden of allergies and asthma, bioaerosols have gained the attention of physicians and researchers over the past decades. However, bioaerosols still remain underestimated, excluded from EU Directives. This work points out that respiratory diseases, an emerging human health risk, may be predicted and appropriately managed only if the entirety of co- and multi-exposures, biogenic as well as mixed (chemical-biological) is considered, especially for vulnerable population groups. Here we present an overview of the state of the art in bioaerosol research and its challenges, and pinpoint unmet research and policy needs in a rapidly changing world.

The EAACI Guidelines used the GRADE approach to evaluate the impact of major indoor air pollutants (dampness and mould, cleaning agents, volatile organic compounds and pesticides) on the risk of new-onset asthma and on asthma-related outcomes. The guideline also acknowledges the synergies among indoor air pollutants and other components of the indoor exposome (allergens, viruses, endotoxins). Very low to low certainty of evidence was found for the association between exposure to indoor pollutants and increased risk of new-onset asthma and asthma worsening. Only for mould exposure there was moderate certainty of evidence for new-onset asthma. Due to the quality of evidence, conditional recommendations were formulated on the risk of exposure to all indoor pollutants. Recommendations are provided for prevention, patient care and mitigation in a framework supporting rational decisions for healthcare professionals and patients to individualize and improve asthma management. For policymakers and regulators this evidence-informed guideline supports setting legally binding standards and goals for indoor air quality at international, national and local levels. Asthma management counselled by the current EAACI guidelines can improve asthma-related outcomes but community and governmental measures for improved indoor air quality are needed to achieve significant impact.

BACKGROUND:Currently, most researchers apply pollen extracts or -suspensions to assess the effects of pollen exposure on airway epithelia. How respiratory epithelia respond to pollen aerosols is not well studied because standardised methods to aerosolize pollen were not available until recently. AIM OF STUDY:To develop and test a near-natural exposure model for pollen grains based on differentiated human nasal epithelial cells and a novel particle aerosoliser. METHODS:Primary human nasal epithelial cells were differentiated at the air-liquid interface and exposed to birch, timothy grass and ragweed pollen, either as aqueous extract, suspension, or particle aerosol generated with the VitroCell PowderX device. Morphology, physical barrier function, and cytokine responses were compared. RESULTS:The cells responded to pollen aerosol exposure with strong mucus production and coordinated ciliary beating in attempt to clear the pollen grains. Pollen aerosols did not affect the transepithelial electrical resistance (TEER), whereas grass pollen extracts led to a significant TEER decrease. Extract exposure resulted in apical and basolateral cytokine release; aerosol exposure led to a directed, predominantly basolateral dose-dependent cytokine response. Cytokine responses to birch, grass and ragweed pollen differed, with birch pollen inducing lower levels of inflammatory cytokines, while timothy and ragweed pollen induced high levels of inflammatory cytokines and alarmins. CONCLUSION:We were able to establish and characterize a biologically relevant pollen aerosol exposure system characterized by a directed cytokine response. The differences in response patterns to different pollen types likely reflect differential sensitisation mechanisms, warranting further research.

BACKGROUND:Symptom monitoring can improve adherence to daily medication. However, controlled clinical trials on multi-modular allergy apps and their various functions have been difficult to implement. The objective of this study was to assess the clinical benefit of an allergy app with varying numbers of functions in reducing symptoms and improving quality of (QoL) life in grass pollen allergic individuals. The secondary objective was to develop a symptom forecast based on patient-derived and environmental data. METHODS:We performed a stratified, controlled intervention study (May-August 2023) with grass pollen allergic participants (N = 167) in Augsburg, Germany. Participants were divided into three groups, each receiving the same allergy app, but with increasing numbers of functions. PRIMARY ENDPOINT:rhinitis-related QoL; Secondary endpoints: symptom scores, relevant behavior, self-reported usefulness of the app, symptom forecast. RESULTS:Rhinitis-related QoL was increased after the intervention, with no statistical inter-group differences. However, participants with access to the full app version, including a pollen forecast, took more medication and reported lower symptoms and social activity impairment than participants with access to a reduced-function app. Using an XGBoost multiclass classification model, we achieved promising results for predicting nasal (accuracy: 0.79; F1-score: 0.78) and ocular (accuracy: 0.82; F1-score: 0.76) symptom levels and derived feature importance using SHAP as a guidance for future approaches. CONCLUSION:Our allergy app with its high-performance pollen forecast, symptom diary, and general allergy-related information provides a clinical benefit for allergy sufferers. Reliable symptom forecasts may be created given high-quality and high-resolution data.

To inform the clinical practice guidelines' recommendations developed by the European Academy of Allergy and Clinical Immunology systematic reviews (SR) assessed using GRADE on the impact of environmental tobacco smoke (ETS) and active smoking on the risk of new-onset asthma/recurrent wheezing (RW)/low lung function (LF), and on asthma-related outcomes. Only longitudinal studies were included, almost all on combustion cigarettes, only one assessing e-cigarettes and LF. According to the first SR (67 studies), prenatal ETS increases the risk of RW (moderate certainty evidence) and may increase the risk of new-onset asthma and of low LF (low certainty evidence). Postnatal ETS increases the risk of new-onset asthma and of RW (moderate certainty evidence) and may impact LF (low certainty evidence). Combined in utero and postnatal ETS may increase the risk of new-onset asthma (low certainty evidence) and increases the risk of RW (moderate certainty evidence). According to the second SR (24 studies), ETS increases the risk of severe asthma exacerbations and impairs asthma control and LF (moderate certainty evidence). According to the third SR (25 studies), active smoking increases the risk of severe asthma exacerbations and of suboptimal asthma control (moderate certainty evidence) and may impact asthma-related quality-of-life and LF (low certainty evidence).

During the birch pollen season an enhanced incidence of virus infections is noticed, raising the question whether pollen can affect anti-viral responses independent of allergic reactions. We previously showed that birch pollentreatment of monocyte-derived dendritic cells (moDC) enhances human cytomegalovirus (HCMV) infection. Here we addressed how in moDC the relatively weak pollen response can affect the comparably strong response to HCMV. To this end, moDC were stimulated with aqueous birch pollen extract (APE), HCMV, and APE with HCMV, and transcriptomic signatures were determined after 6 and 24 h of incubation. Infection was monitored upon exposure of moDC to GFP expressing HCMV by flow cytometric analysis of GFP expressing cells. Principle component analysis of RNA sequencing data revealed close clustering of mock and APE treated moDC, whereas HCMV as well as APE with HCMV treated moDC clustered separately after 6 and 24 h of incubation, respectively. Communally induced genes were detected in APE, HCMV and APE with HCMV treated moDC. In APE with HCMV treated moDC, the comparably weak APE induced signatures were maintained after HCMV exposure. In particular, NF-xB/RELA and PI3K/AKT/MAPK signaling were altered upon APE with HCMV exposure. Earlier, we discovered that NF-xB inhibition alleviated APE induced enhancement of HCMV infection. Here we additionally found that impairment of PI3K signaling reduced HCMV infection in HCMV and APE with HCMV treated moDC. APE treated moDC that were exposed to HCMV show a unique host gene signature, which to a large extent is regulated by NF-xB activation and PI3K/AKT/MAPK signaling.

Background: Whilst SARS-CoV-2 infection has become endemic, COVID-19 related hospitalization and mortality are still considerably high. Both anti-viral and immune modulating therapies against COVID-19 are available, but they must be initiated early after infection and given only to patients of need. Currently, patients demographics and clinical pre-conditions factors are used to determine treatment eligibility. However, the latter do not provide accurate prediction and there are no useful biomarkers for early accurate prediction of COVID-19 related hospitalization risk and disease progression. Methods: Non-vaccinated patients (N=185) were recruited early after the first positive SARS-CoV-2 test. Biochemistry, hematology and 8 serum cytokine levels were longitudinally measured within the first month. Findings: Early levels of LDH, IL-6 or CRP each alone or their combinations, were identified as accurate predictors for the risk of hospitalization (sensitivity=93.6-100%, specificity=93.4-96.7%, p<0.0001). Moreover, the combination of 4 cytokines (IFN-α, IFN-γ, IL-6, IL-17A) was the only accurate predictor for symptoms risk (sensitivity=97.5%, specificity=92.3%, p<0.0001). In comparison, age and BMI showed significantly lower predictive values than above biomarkers. Prediction with above biomarkers was independent of sampling time (0-11 days post symptoms onset), age, gender, BMI, clinical pre-conditions or SARS-CoV-2 variant. Furthermore, the early higher levels of LDH, CRP and inflammatory cytokines in hospitalized, as compared to non-hospitalized, patients, stayed consistently higher for at least 4 weeks. Interpretation: The risk for COVID-19 hospitalization or symptoms can be accurately predicted as early as the time of the first positive SARS-CoV-2 test, with biomarkers that are feasibly measurable at point-of-testing. These findings could allow for better early personalized treatment and optimization of clinical management of COVID-19 patients. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the Bavarian State Ministry for Science and Art Program for the funding of Corona research (Early-Opt-COVID19 project and research networks FOR-COVID and Bay-VOC), by grants from the Helmholtz Association Initiative and Networking Fund (KA1-Co-02 COVIPA to UP; KA1-Co-06 CORAERO to CH, MG and AUN), by the European Commission FET Open Grant VIROFIGHT (grant no. 899619), and by the Sanddorf foundation. Work in the Gorochov laboratory was supported by Institut National de la Sante et de la Recherche Medicale (INSERM), Sorbonne Universite, Fondation pour la Recherche Medicale (FRM), Paris, France, program Investissement d Avenir launched by the French Government and implemented by the Agence Nationale de la Recherche(ANR) (programme COFIFERON ANR-21-RHUS-08), by EU Horizon HLTH-2021-DISEASE-04UNDINE project, by Fondation pour la Recherche Medicale, Paris, France (programme Equipe FRM 2022) and by the Departement Medico-Universitairede Biologie et Genomique Medicales (DMU BioGen), APHP, Paris, France. We thank the PerForM-REACT Project (funded by the Free State of Bavaria and the European Regional Development Fund - ERDF) for use of devices and consumables. The French-German collaboration was additionally supported by the BayFrance foundation. UP received personal fees from Abbott, Abbvie, Arbutus, Gilead, GSK, Leukocare, J&J, Roche, MSD, Sanofi, Sobi and Vaccitech. UP is a co-founder and share-holder of SCG Cell Therapy. All other authors declare no conflict of interest. The study was independently designed, run, analyzed and summarized by the authors with no involvement from the funding agencies. The manuscript was written by the authors with no involvement of the funding agencies. The funding agencies did not pay for or were involved in any way of writing the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of the Technical University of Munich gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.

The EAACI Guidelines on the impact of short-term exposure to outdoor pollutants on asthma-related outcomes provide recommendations for prevention, patient care and mitigation in a framework supporting rational decisions for healthcare professionals and patients to individualize and improve asthma management and for policymakers and regulators as an evidence-informed reference to help setting legally binding standards and goals for outdoor air quality at international, national and local levels. The Guideline was developed using the GRADE approach and evaluated outdoor pollutants referenced in the current Air Quality Guideline of the World Health Organization as single or mixed pollutants and outdoor pesticides. Short-term exposure to all pollutants evaluated increases the risk of asthma-related adverse outcomes, especially hospital admissions and emergency department visits (moderate certainty of evidence at specific lag days). There is limited evidence for the impact of traffic-related air pollution and outdoor pesticides exposure as well as for the interventions to reduce emissions. Due to the quality of evidence, conditional recommendations were formulated for all pollutants and for the interventions reducing outdoor air pollution. Asthma management counselled by the current EAACI guidelines can improve asthma-related outcomes but global measures for clean air are needed to achieve significant impact.

The high prevalence of hay fever in Europe has raised concerns about the implications of climate change-induced higher temperatures on pollen production. Our study focuses on downy birch pollen production across Europe by analyzing 456 catkins during 2019-2021 in 37 International Phenological Gardens (IPG) spanning a large geographic gradient. As IPGs rely on genetically identical plants, we were able to reduce the effects of genetic variability. We studied the potential association with masting behavior and three model specifications based on mean and quantile regression to assess the impact of meteorology (e.g., temperature and precipitation) and atmospheric gases (e.g., ozone (O3) and carbon-dioxide (CO2)) on pollen and catkin production, while controlling for tree age approximated by stem circumference. The results revealed a substantial geographic variability in mean pollen production, ranging from 1.9 to 2.5 million pollen grains per catkin. Regression analyses indicated that elevated average temperatures of the previous summer corresponded to increased pollen production, while higher O3 levels led to a reduction. Additionally, catkins number was positively influenced by preceding summer's temperature and precipitation but negatively by O3 levels. The investigation of quantile effects revealed that the impacts of mean temperature and O3 levels from the previous summer varied throughout the conditional response distribution. We found that temperature predominantly affected trees characterized by a high pollen production. We therefore suggest that birches modulate their physiological processes to optimize pollen production under varying temperature regimes. In turn, O3 levels negatively affected trees with pollen production levels exceeding the conditional median. We conclude that future temperature increase might exacerbate pollen production while other factors may modify (decrease in the case of O3 and amplify for precipitation) this effect. Our comprehensive study sheds light on potential impacts of climate change on downy birch pollen production, which is crucial for birch reproduction and human health.