Comparison of two different pollen season definitions based on 10 years of birch and grass pollen data from two distant central European cities: An EAACI Task Force report

Abstract

Start, duration, and intensity of different pollen seasons (PSs) can significantly differ between countries and regions with a high grade of annual variety over the longitudinal course.¹ This is mainly influenced by factors such as climate, vegetation, urbanization, pollution, and others. The documentation of long-term changes in pollen flight is influenced by the method used to define a PS.

Airborne pollen is measured commonly using Hirst-type volumetric spore traps² according to national³ and European Union standards.⁴ The results are usually expressed as average daily pollen concentrations of different pollen taxa (in pollen grains/m³ of air), which can be used to calculate the start and end of the PS. However, the above-mentioned variability of confounding factors is an obstacle to an overarching, generally accepted definition.¹ Several PS definitions, serving difference scientific purposes, are in use,⁵ but have not been validated with respect to allergen immunotherapy (AIT).⁶

In 2017, the European Academy of Allergy and Clinical Immunology (EAACI) published a Position Paper with threshold definitions for the start of PS, peak pollen period(s) (PPP[s]), high pollen day(s), and end of PS depending on the measured daily pollen concentrations and for the following pollen taxa: grasses, birch, olive, cypress, and ragweed.⁷ This definition was found to correlate significantly with the Total Nasal Symptom and Medication Score for grass and birch pollen-induced allergic rhinitis reported by users of electronic diaries (patient hay fever diaries [PHDs]) in Germany⁸ as well as in Finland, Austria, and France.⁹ Besides, defining a percentage of the seasonal pollen integral as start and end date as suggested by the European Aeroallergen Network (EAN) was found to be useful only in regions with exceptionally low pollen concentrations (so called percentage analysis [PA] in the following text).¹

The subsequent analysis of our EAACI Task Force on “Definition of clinical relevant thresholds of allergen exposure for analysis of outcomes in AIT” aimed to compare the two PS definition methods described above—EAACI and PA—when applied to 10 years of pollen data from the two distant cities of Berlin, Germany and Vienna, Austria, with the beeline between the cities being 524 km.

Birch and grass pollen concentrations were continuously monitored (2013–2022) in both cities using the monitoring method described above with Berlin showing higher pollen concentration compared to Vienna for both pollen taxa (Figure 1). The available data were used to conduct the following analyses for comparing the two PS methods: (i) start, end, and duration of PS (Figure 2), PPP(s), and high pollen day(s), and (ii) start days of the respective time intervals.

For the PS start (Figure 2A) based on the EAACI PS definition, the calculation showed that the grass PS started over the 10-year period on average approximately 7 days earlier in Vienna than in Berlin and with a slightly lower spread of the day. The analysis using PA also mirrored that the start of the grass PS was earlier while the difference to Berlin was approximately 10 days. For birch pollen, the difference in the PS start between Vienna and Berlin was approximately 2 days according to the EAACI definition and approximately 5 days according to the PA with Vienna demonstrating the earlier start in both cases. The results suggest a slightly later PS start for both pollen taxa and locations when the PA method is used in comparison to the EAACI definition. The earlier occurrence of PS start for both taxa in Vienna, in comparison to Berlin, regardless of the definition applied, is summarized in supplementary material (Figure S1).

The beginning of the first (if many) or the single (if only one) PPP for birch was also on average 5 days earlier in Vienna than in Berlin, with a mean total duration of the PPP(s), for those years that demonstrated at least one PPP of 19 days in Berlin and 15 days in Vienna. In a similar approach and for grass pollen, the beginning of the PPP(s) occurred approximately 4 days earlier in Vienna than in Berlin, with a mean duration for those years that demonstrated at least one PPP of 23 days in Berlin and 12 days in Vienna.

The high pollen days for grasses and birch according to the EAACI definition (i.e., those days with at least 50 grass pollen/m³ of air and at least 100 birch pollen/m³ of air) were on average 17 and 23 for grasses and 15 and 21 for birch in Vienna and Berlin, respectively. In addition, the peak dates (i.e., the date where the maximum pollen concentration appears), occurs later in Berlin in comparison to Vienna (Figure S1) for both taxa.

For the PS end (Figure 2B), the EAACI definition led to an earlier PS end in Vienna compared to Berlin for grass (approximately 12 days) and birch pollen (approximately 14 days) which was partly confirmed by the PA: with this method, an approximate 6 days earlier end was found for birch in Vienna, but an approximate 10 days later end for grass, on average.

Concerning the PS duration (Figure 2C), the application of the EAACI definition resulted in a 6-day longer grass PS in Berlin and to a 12-day longer birch PS, in comparison to Vienna on average, with a lower spread of days for Berlin. For PA, the duration of the grass PS was longer in Vienna than in Berlin (by approximately 20 days on average), while the difference for the birch PS was negligible. The difference between the PS start for grass, for both Berlin and Vienna, as resulting from the two PS definition methods (PA and EAACI), was found to be statistically significant (p = .02 for both cities). The difference in the other PS characteristics between the two PS definition methods was not found to be statistically significant, for neither grass nor birch, regardless of the city under investigation.

Our analysis confirmed previous reports⁹ using the EAACI definition⁷ that differences of onset and end of PS as well as PPP(s) in distant European regions can be appropriately evaluated with the EAACI definition, now demonstrated over a longer time course of 10 years of pollen data from Berlin and Vienna.

The concise information on the start and end of the PS is of utmost importance, for example, for planning the initiation of AIT, which is usually recommended within an ample time frame before the respective PS in order to be efficacious and safe. Knowledge of the start of the respective PS is also of great importance for the design of clinical trials in AIT aiming to read-out benefits of the treatment within the ideal timeframe.⁶

The presented analysis of pollen data confirmed that the EAACI definition of the PS is applicable to distant areas and may lead to different starting time-points locally. Also differences in the onset and the length of the PPPs were found between the two studied areas, which underlines the importance of determining this interval in accordance with the local pollen flight. As the highest clinical effect sizes in AIT can be found in days of highest pollen-exposure, attention should be paid to these differences in distant regions as those will highly impact the outcomes of clinical trials in AIT.¹⁰

Second, the analysis in this letter aimed to compare the EAACI PS definition⁷ with the PA as recommended by the EAN.¹ Our results confirmed a high degree of coherence between these two PS definitions over a 10-year follow-up period. However, as previously reported⁹ the EAACI definition may better apply to the clinical requirements, for example, for clinical trial design. Nevertheless, differences of the two definitions regarding the defined time-periods observed in the analysis of the 10-year pollen data mirror reports from an analysis for a Mediterranean region.¹¹ As outlined above, the PA characterizes respective time intervals post-hoc based on whole year pollen data, which is not useful for prospective clinical trials, for example, in AIT. In contrast, the EAACI definition considers the most recent data on daily pollen concentrations of the relevant pollen taxa for application, for example, in clinical trials of AIT aimed at demonstrating clinical effect sizes in the relevant time periods of pollen exposure.⁹

In conclusion, our analysis of birch and grass pollen data collected continuously over a long observation period of 10 years in two distant central European cities confirmed the applicability of the both approaches—the PA and the EAACI definition—to describe PS characteristics for both pollen taxa and both areas. The PA is applied only after a full year of pollen monitoring and the EAACI definition provides the possibility to (a) determine clinically relevant PS characteristics (b) already during the respective PS. These results have important implications for preventive health care and treatment of allergic patients with pollen-related seasonal allergies and will also support the design of clinical trials on the ideal timing of AIT performing and monitoring.

B. Werchan and M. Werchan provided the pollen data from Berlin, Germany. U. E. Berger and M. Bastl provided the pollen data from Vienna, Austria. K. Karatzas and T. Tasioulis carried out the statistical analysis. O. Pfaar and K.C. Bergmann drafted the first version of the article. All authors reviewed and revised the article and gave their final approval for submission of this article. Hereafter, all members of the EAACI Task Force “Definition of clinical relevant thresholds of allergen exposure for analysis of outcomes in AIT” have finally reviewed the article and have given approval for the submission of this article to the journal Allergy.

This Task-Force report was supported by the European Academy of Allergy and Clinical Immunology (EAACI) under the EAACI Task Force “Definition of clinical relevant thresholds of allergen exposure for analysis of outcomes in AIT”, budget code number: 40904, 2022–23.

OP reports grants and/or personal fees and/or travel support from ALK-Abelló, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, Laboratorios LETI/LETI Pharma, GlaxoSmithKline, ROXALL Medizin, Novartis, Sanofi-Aventis and Sanofi-Genzyme, Med Update Europe GmbH, streamedup! GmbH, Pohl-Boskamp, Inmunotek S.L., John Wiley and Sons/AS, Paul-Martini-Stiftung (PMS), Regeneron Pharmaceuticals Inc., RG Aerztefortbildung, Institut für Disease Management, Springer GmbH, AstraZeneca, IQVIA Commercial, Ingress Health, Wort&Bild Verlag, Verlag ME, Procter&Gamble, ALTAMIRA, Meinhardt Congress GmbH, Deutsche Forschungsgemeinschaft, Thieme, Deutsche AllergieLiga e.V., AeDA, Alfried-Krupp Krankenhaus, Red Maple Trials Inc., Königlich Dänisches Generalkonsulat, Medizinische Hochschule Hannover, ECM Expro&Conference Management, Technical University Dresden, Lilly, Japanese Society of Allergy, Forum für Medizinische Fortbildung, Dustri-Verlag, Pneumolive, ASIT Biotech, LOFARMA, Almirall, Paul-Ehrlich-Institut, outside the submitted work; and he is Vice President of EAACI and member of EAACI Excom, member of ext. board of directors DGAKI; coordinator, main- or co-author of different position papers and guidelines in rhinology, allergology and allergen-immunotherapy; he is associate editor (AE) of Allergy and Clinical Translational Allergy. All other authors report no conflict of interest.