O. Pfaar, M. Bastl, M. Berger, U. E. Berger, K. Karatzas, T. Tasioulis, B. Werchan, M. Werchan, K. C. Bergmann, for the EAACI Task Force “Definition of clinical relevant thresholds of allergen exposure for analysis of outcomes in AIT”
{"title":"根据欧洲中部两个偏远城市 10 年的桦树和草花粉数据,比较两种不同的花粉季节定义:EAACI 特别工作组报告。","authors":"O. Pfaar, M. Bastl, M. Berger, U. E. Berger, K. Karatzas, T. Tasioulis, B. Werchan, M. Werchan, K. C. Bergmann, for the EAACI Task Force “Definition of clinical relevant thresholds of allergen exposure for analysis of outcomes in AIT”","doi":"10.1111/all.16252","DOIUrl":null,"url":null,"abstract":"<p>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.<span><sup>1</sup></span> 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.</p><p>Airborne pollen is measured commonly using Hirst-type volumetric spore traps<span><sup>2</sup></span> according to national<span><sup>3</sup></span> and European Union standards.<span><sup>4</sup></span> The results are usually expressed as average daily pollen concentrations of different pollen taxa (in pollen grains/m<sup>3</sup> 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.<span><sup>1</sup></span> Several PS definitions, serving difference scientific purposes, are in use,<span><sup>5</sup></span> but have not been validated with respect to allergen immunotherapy (AIT).<span><sup>6</sup></span></p><p>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.<span><sup>7</sup></span> 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 Germany<span><sup>8</sup></span> as well as in Finland, Austria, and France.<span><sup>9</sup></span> 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).<span><sup>1</sup></span></p><p>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.</p><p>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.</p><p>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).</p><p>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.</p><p>The high pollen days for grasses and birch according to the EAACI definition (i.e., those days with at least 50 grass pollen/m<sup>3</sup> of air and at least 100 birch pollen/m<sup>3</sup> 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.</p><p>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.</p><p>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 (<i>p</i> = .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.</p><p>Our analysis confirmed previous reports<span><sup>9</sup></span> using the EAACI definition<span><sup>7</sup></span> 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.</p><p>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.<span><sup>6</sup></span></p><p>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.<span><sup>10</sup></span></p><p>Second, the analysis in this letter aimed to compare the EAACI PS definition<span><sup>7</sup></span> with the PA as recommended by the EAN.<span><sup>1</sup></span> Our results confirmed a high degree of coherence between these two PS definitions over a 10-year follow-up period. However, as previously reported<span><sup>9</sup></span> 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.<span><sup>11</sup></span> 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.<span><sup>9</sup></span></p><p>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.</p><p>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 <i>Allergy</i>.</p><p>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.</p><p>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.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"79 11","pages":"3161-3165"},"PeriodicalIF":12.6000,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16252","citationCount":"0","resultStr":"{\"title\":\"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\",\"authors\":\"O. Pfaar, M. Bastl, M. Berger, U. E. Berger, K. Karatzas, T. Tasioulis, B. Werchan, M. Werchan, K. C. Bergmann, for the EAACI Task Force “Definition of clinical relevant thresholds of allergen exposure for analysis of outcomes in AIT”\",\"doi\":\"10.1111/all.16252\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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.<span><sup>1</sup></span> 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.</p><p>Airborne pollen is measured commonly using Hirst-type volumetric spore traps<span><sup>2</sup></span> according to national<span><sup>3</sup></span> and European Union standards.<span><sup>4</sup></span> The results are usually expressed as average daily pollen concentrations of different pollen taxa (in pollen grains/m<sup>3</sup> 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.<span><sup>1</sup></span> Several PS definitions, serving difference scientific purposes, are in use,<span><sup>5</sup></span> but have not been validated with respect to allergen immunotherapy (AIT).<span><sup>6</sup></span></p><p>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.<span><sup>7</sup></span> 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 Germany<span><sup>8</sup></span> as well as in Finland, Austria, and France.<span><sup>9</sup></span> 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).<span><sup>1</sup></span></p><p>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.</p><p>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.</p><p>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).</p><p>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.</p><p>The high pollen days for grasses and birch according to the EAACI definition (i.e., those days with at least 50 grass pollen/m<sup>3</sup> of air and at least 100 birch pollen/m<sup>3</sup> 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.</p><p>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.</p><p>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 (<i>p</i> = .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.</p><p>Our analysis confirmed previous reports<span><sup>9</sup></span> using the EAACI definition<span><sup>7</sup></span> 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.</p><p>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.<span><sup>6</sup></span></p><p>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.<span><sup>10</sup></span></p><p>Second, the analysis in this letter aimed to compare the EAACI PS definition<span><sup>7</sup></span> with the PA as recommended by the EAN.<span><sup>1</sup></span> Our results confirmed a high degree of coherence between these two PS definitions over a 10-year follow-up period. However, as previously reported<span><sup>9</sup></span> 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.<span><sup>11</sup></span> 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.<span><sup>9</sup></span></p><p>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.</p><p>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 <i>Allergy</i>.</p><p>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.</p><p>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.</p>\",\"PeriodicalId\":122,\"journal\":{\"name\":\"Allergy\",\"volume\":\"79 11\",\"pages\":\"3161-3165\"},\"PeriodicalIF\":12.6000,\"publicationDate\":\"2024-08-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16252\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Allergy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/all.16252\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ALLERGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Allergy","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/all.16252","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ALLERGY","Score":null,"Total":0}
引用次数: 0
摘要
就 PS 结束时间而言(图 2B),采用 EAACI 定义,维也纳的草地(约 12 天)和桦树花粉(约 14 天)的 PS 结束时间比柏林早,这一点在 PA 中得到了部分证实:采用这种方法,维也纳的桦树花粉结束时间比柏林早约 6 天,而草地花粉结束时间平均晚约 10 天。关于 PS 持续时间(图 2C),与维也纳相比,采用 EAACI 定义后,柏林的草地 PS 延长了 6 天,桦树 PS 延长了 12 天,但柏林的天数分布较低。就 PA 而言,维也纳的草地 PS 持续时间比柏林长(平均长约 20 天),而桦树 PS 的差异可以忽略不计。根据两种 PS 定义方法(PA 和 EAACI),柏林和维也纳的草地 PS 开始时间之间的差异具有显著的统计学意义(两座城市的 p = 0.02)。我们的分析证实了之前使用 EAACI 定义9 的报告7 ,即使用 EAACI 定义可以适当评估欧洲遥远地区 PS 开始和结束以及 PPP 的差异。有关 PS 开始和结束的简明信息至关重要,例如,对于规划启动 AIT(通常建议在相应 PS 开始前的充裕时间内启动 AIT,以确保其有效性和安全性)来说就是如此。了解相应的 PS 开始时间对于设计旨在在理想时间框架内读出治疗效果的 AIT 临床试验也非常重要。6 对花粉数据的分析证实,EAACI 对 PS 的定义适用于遥远地区,但可能导致当地的开始时间点不同。此外,两个研究地区的 PPP 开始时间和持续时间也存在差异,这凸显了根据当地花粉飞行情况确定该时间间隔的重要性。10 其次,这封信中的分析旨在比较 EAACI PS 定义7 和 EAN 推荐的 PA。然而,正如之前所报道的那样9 ,EAACI 的定义可能更适用于临床要求,例如临床试验设计。尽管如此,在 10 年花粉数据分析中观察到的两种定义在定义时间段上的差异反映了地中海地区的分析报告。11 如上所述,PA 根据全年花粉数据对各自的时间段进行了事后描述,这对于前瞻性临床试验(如 AIT)并无用处。与此相反,EAACI 定义考虑了相关花粉类群每日花粉浓度的最新数据,可用于例如旨在证明花粉暴露相关时间段内临床效应大小的 AIT 临床试验。9 总之,我们对在两个遥远的欧洲中部城市 10 年长期观察期间连续收集的桦树和草花粉数据进行了分析,结果证实 PA 和 EAACI 定义这两种方法都适用于描述两种花粉类群和两个地区的 PS 特征。PA 只有在一整年的花粉监测后才能应用,而 EAACI 定义则提供了(a)确定临床相关的 PS 特征(b)在相应的 PS 期间就能应用的可能性。这些结果对花粉相关季节性过敏患者的预防保健和治疗具有重要意义,也将有助于设计有关 AIT 执行和监测的理想时机的临床试验。U. E. Berger 和 M. Bastl 提供了奥地利维也纳的花粉数据。K. Karatzas 和 T. Tasioulis 进行了统计分析。O. Pfaar 和 K.C. Bergmann 起草了文章的第一版。所有作者对文章进行了审阅和修改,并最终同意提交本文。此后,EAACI "用于分析 AIT 结果的过敏原暴露临床相关阈值的定义 "工作组的所有成员对文章进行了最终审阅,并同意将本文提交至《过敏》杂志。 本工作组报告得到了欧洲过敏与临床免疫学学会(EAACI)"用于分析 AIT 结果的过敏原暴露临床相关阈值的定义 "工作组的支持,预算代码:40904,2022-23。OP 报告了 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 和 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, Forumür 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.他是 EAACI 副主席和 EAACI Excom 成员,DGAKI 董事会临时成员;鼻病学、过敏学和过敏原免疫疗法领域不同立场文件和指南的协调人、主要作者或合著者;他是《过敏》和《临床转化过敏》杂志的副主编 (AE)。所有其他作者均未报告利益冲突。
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
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.
期刊介绍:
Allergy is an international and multidisciplinary journal that aims to advance, impact, and communicate all aspects of the discipline of Allergy/Immunology. It publishes original articles, reviews, position papers, guidelines, editorials, news and commentaries, letters to the editors, and correspondences. The journal accepts articles based on their scientific merit and quality.
Allergy seeks to maintain contact between basic and clinical Allergy/Immunology and encourages contributions from contributors and readers from all countries. In addition to its publication, Allergy also provides abstracting and indexing information. Some of the databases that include Allergy abstracts are Abstracts on Hygiene & Communicable Disease, Academic Search Alumni Edition, AgBiotech News & Information, AGRICOLA Database, Biological Abstracts, PubMed Dietary Supplement Subset, and Global Health, among others.