Tari Haahtela, Liam O'Mahony, Claudia Traidl‐Hoffmann, Mubeccel Akdis, Ozlem Ceylan, Panagiotis Chaslaridis, Athanasios Damialis, Stefano Del Giacco, Antti Lauerma, Kari C. Nadeau, Inês Paciência, Isabella Pali‐Schöll, Oscar Palomares, Harald Renz, Jurgen Schwarze, Marilyn Urrutia‐Pereira, Carina Venter, Donata Vercelli, Tonya Winders, Cezmi A. Akdis, Marek Jutel, Ioana Agache
The allergy and asthma epidemic in urban societies following World War II is mostly caused by changes in the environment, diet and lifestyle. Disconnection of urban populations from the wider environment has reduced the protective factors building up immunological resilience. The European Academy of Allergy and Clinical Immunology (EAACI) guidelines on greenness impact on allergy and asthma follow the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach and provide eight recommendations encouraging greenness exposure to support immune health. Controlled follow‐up studies are still scarce, and the strength of evidence is generally low or moderate at best. For primary prevention of allergy and asthma, most of the evidence indicates beneficial effects. Exposure is also useful for secondary prevention. Asthma patients may feel better and need less medication by combining green space exposure with physical activity. During the high‐pollen season, effective seasonal medication is necessary for patients with pollen allergy. In urban planning, implementing appropriate green infrastructure and easy access to green space promotes immune health and reduces risks of air pollution and heatwaves. These EAACI guidelines are the first recommendations highlighting the importance of urban green spaces on immune health and call for prioritising innovative research in this field.
{"title":"EAACI Guidelines on the Importance of Green Space in Urban Environments for Allergy and Asthma Prevention","authors":"Tari Haahtela, Liam O'Mahony, Claudia Traidl‐Hoffmann, Mubeccel Akdis, Ozlem Ceylan, Panagiotis Chaslaridis, Athanasios Damialis, Stefano Del Giacco, Antti Lauerma, Kari C. Nadeau, Inês Paciência, Isabella Pali‐Schöll, Oscar Palomares, Harald Renz, Jurgen Schwarze, Marilyn Urrutia‐Pereira, Carina Venter, Donata Vercelli, Tonya Winders, Cezmi A. Akdis, Marek Jutel, Ioana Agache","doi":"10.1111/all.70182","DOIUrl":"https://doi.org/10.1111/all.70182","url":null,"abstract":"The allergy and asthma epidemic in urban societies following World War II is mostly caused by changes in the environment, diet and lifestyle. Disconnection of urban populations from the wider environment has reduced the protective factors building up immunological resilience. The European Academy of Allergy and Clinical Immunology (EAACI) guidelines on greenness impact on allergy and asthma follow the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach and provide eight recommendations encouraging greenness exposure to support immune health. Controlled follow‐up studies are still scarce, and the strength of evidence is generally low or moderate at best. For primary prevention of allergy and asthma, most of the evidence indicates beneficial effects. Exposure is also useful for secondary prevention. Asthma patients may feel better and need less medication by combining green space exposure with physical activity. During the high‐pollen season, effective seasonal medication is necessary for patients with pollen allergy. In urban planning, implementing appropriate green infrastructure and easy access to green space promotes immune health and reduces risks of air pollution and heatwaves. These EAACI guidelines are the first recommendations highlighting the importance of urban green spaces on immune health and call for prioritising innovative research in this field.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"6 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145731022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nami Shrestha Palikhe, Yingqi Wu, Karen J. Howie, Caitlin Stevens, Jennifer Mitchell, Lesley Wiltshire, Gail M. Gauvreau, Harissios Vliagoftis
{"title":"Monocyte Chemotactic Factors in the Airways of Patients With Mild Asthma Before and After an Allergen Challenge","authors":"Nami Shrestha Palikhe, Yingqi Wu, Karen J. Howie, Caitlin Stevens, Jennifer Mitchell, Lesley Wiltshire, Gail M. Gauvreau, Harissios Vliagoftis","doi":"10.1111/all.70192","DOIUrl":"https://doi.org/10.1111/all.70192","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"143 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145730992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shahriyar Shahbazi Khamas, Paul Brinkman, Jelle M Blankestijn, Aruna T Bansal, Nazanin Zounemat-Kermani, Mahmoud I Abdel-Aziz, Anke H Maitland-van der Zee
{"title":"Reply to Correspondence: Accuracy Is Not Enough: Stability-Aware Feature Selection for Reproducible Biomarker Discovery.","authors":"Shahriyar Shahbazi Khamas, Paul Brinkman, Jelle M Blankestijn, Aruna T Bansal, Nazanin Zounemat-Kermani, Mahmoud I Abdel-Aziz, Anke H Maitland-van der Zee","doi":"10.1111/all.70193","DOIUrl":"https://doi.org/10.1111/all.70193","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":12.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comprehensive Analysis of Food Allergy Research Trends via Large Language Model-Assisted Text Mining (1980-2024).","authors":"Yoshiyuki Kobayashi,Takahiro Inoue,Itsuki Kageyama,Yusuke Iwasaki,Rie Ito,Kota Kodama,Hiroshi Akiyama","doi":"10.1111/all.70169","DOIUrl":"https://doi.org/10.1111/all.70169","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"8 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lian F. van der Gang, Celeste M. Boesjes, Nicolaas P. A. Zuithoff, Inge Haeck, Octavian Bacoş‐Cosma, Laura Loman, Keneshka Atash, Veroniek Harbers, Simone Stadhouders, Albert J. Oosting, Anneke M. T. van Lynden‐van Nes, Klaziena Politiek, Antoni Gostynski, Wianda A. Christoffers, Floor M. Garritsen, Annebeth Flinterman, Wouter R. H. Touwslager, Berit Velstra, Shiarra M. Stewart, Francine C. van Erp, Annemie F. S. Galimont‐Collen, Marie‐Louise A. Schuttelaar, Marlies de Graaf, Marjolein S. de Bruin‐Weller
{"title":"Drug Survival in Atopic Dermatitis: Comparison of Biologics and JAK Inhibitors in the BioDay Registry","authors":"Lian F. van der Gang, Celeste M. Boesjes, Nicolaas P. A. Zuithoff, Inge Haeck, Octavian Bacoş‐Cosma, Laura Loman, Keneshka Atash, Veroniek Harbers, Simone Stadhouders, Albert J. Oosting, Anneke M. T. van Lynden‐van Nes, Klaziena Politiek, Antoni Gostynski, Wianda A. Christoffers, Floor M. Garritsen, Annebeth Flinterman, Wouter R. H. Touwslager, Berit Velstra, Shiarra M. Stewart, Francine C. van Erp, Annemie F. S. Galimont‐Collen, Marie‐Louise A. Schuttelaar, Marlies de Graaf, Marjolein S. de Bruin‐Weller","doi":"10.1111/all.70187","DOIUrl":"https://doi.org/10.1111/all.70187","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"29 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joana Antão,Guilherme Rodrigues,Nazanin Zounemat-Kermani,Paolo Montuschi,Qichen Deng,Frits M E Franssen,Lars I Andersson,Ian M Adcock,Sven-Erik Dahlén,Scott S Wagers,Martijn A Spruit,Alda Marques,
BACKGROUNDControlling asthma symptoms remains challenging. Understanding its molecular mechanisms may provide new insights into asthma pathophysiology. We explored the associations between the transcriptome and proteome in blood and sputum and asthma symptom control.METHODSThis cross-sectional study included asthmatic and healthy adults from the U-BIOPRED cohort. Uncontrolled symptoms were defined as a mean ≥ 1.5 points on the 5-item asthma control questionnaire. Stability selection using LASSO logistic regression identified genes/proteins associated with symptom control, followed by logistic regression. Analyses were adjusted for age, sex, age of asthma onset, smoking status, body mass index (BMI), FEV1% predicted, exacerbation history, anti-IgE therapy and urinary steroid levels. The selected variables were compared with healthy controls using linear regression, adjusted for age, sex, BMI, smoking status and urinary steroid levels.RESULTSFour serum proteins were selected based on data from 415 asthmatics (median age 52 [41, 61] years; 59% female; 64% uncontrolled). Higher TWEAKR/TNFRSF12A [OR 2.25 (95% CI 1.15, 4.77)] and MBL/MBP-C [1.6 (1.07, 2.42)] levels increased the odds of uncontrolled symptoms, whereas higher MK08/MAPK8 [0.48 (0.29, 0.76)] and CD5L [0.59 (0.41, 0.82)] levels decreased the odds. CD5L levels were significantly lower in severe asthma than in healthy controls [estimate -0.23 (95% CI -0.41, -0.04)]. No associations were found between symptom control and the sputum proteome (N = 90) or the sputum (N = 96) and blood (N = 360) transcriptomes.CONCLUSIONFour serum proteins distinguished asthmatics with uncontrolled from controlled symptoms. CD5L levels were also lower in asthmatics with severe disease than in healthy controls, warranting further investigation into its potential therapeutic value.
背景：控制哮喘症状仍然具有挑战性。了解其分子机制可能为哮喘病理生理学提供新的见解。我们探讨了血液和痰中转录组和蛋白质组与哮喘症状控制之间的关系。方法本横断面研究包括来自U-BIOPRED队列的哮喘和健康成人。未控制症状定义为在5项哮喘控制问卷中平均≥1.5分。使用LASSO逻辑回归进行稳定性选择，确定与症状控制相关的基因/蛋白质，然后进行逻辑回归。分析调整了年龄、性别、哮喘发病年龄、吸烟状况、体重指数（BMI）、预测FEV1%、加重史、抗ige治疗和尿类固醇水平。选择的变量与健康对照使用线性回归进行比较，调整年龄、性别、BMI、吸烟状况和尿类固醇水平。结果从415例哮喘患者（中位年龄52岁[41,61]，女性59%，未控制者64%）中选择4种血清蛋白。较高的TWEAKR/TNFRSF12A [OR 2.25 (95% CI 1.15, 4.77)]和MBL/MBP-C[1.6(1.07, 2.42))]水平增加了症状失控的几率，而较高的MK08/MAPK8[0.48(0.29, 0.76)]和CD5L[0.59(0.41, 0.82)]水平降低了症状失控的几率。严重哮喘患者的CD5L水平显著低于健康对照组[估计值-0.23 (95% CI -0.41, -0.04)]。症状控制与痰蛋白组（N = 90）或痰转录组（N = 96）和血转录组（N = 360）之间没有关联。结论4种血清蛋白可区分哮喘控制症状与控制症状。患有严重疾病的哮喘患者的CD5L水平也低于健康对照组，值得进一步研究其潜在的治疗价值。
{"title":"Proteomic and Transcriptomic Signatures of Poor Asthma Symptom Control in the U-BIOPRED Cohort.","authors":"Joana Antão,Guilherme Rodrigues,Nazanin Zounemat-Kermani,Paolo Montuschi,Qichen Deng,Frits M E Franssen,Lars I Andersson,Ian M Adcock,Sven-Erik Dahlén,Scott S Wagers,Martijn A Spruit,Alda Marques, ","doi":"10.1111/all.70178","DOIUrl":"https://doi.org/10.1111/all.70178","url":null,"abstract":"BACKGROUNDControlling asthma symptoms remains challenging. Understanding its molecular mechanisms may provide new insights into asthma pathophysiology. We explored the associations between the transcriptome and proteome in blood and sputum and asthma symptom control.METHODSThis cross-sectional study included asthmatic and healthy adults from the U-BIOPRED cohort. Uncontrolled symptoms were defined as a mean ≥ 1.5 points on the 5-item asthma control questionnaire. Stability selection using LASSO logistic regression identified genes/proteins associated with symptom control, followed by logistic regression. Analyses were adjusted for age, sex, age of asthma onset, smoking status, body mass index (BMI), FEV1% predicted, exacerbation history, anti-IgE therapy and urinary steroid levels. The selected variables were compared with healthy controls using linear regression, adjusted for age, sex, BMI, smoking status and urinary steroid levels.RESULTSFour serum proteins were selected based on data from 415 asthmatics (median age 52 [41, 61] years; 59% female; 64% uncontrolled). Higher TWEAKR/TNFRSF12A [OR 2.25 (95% CI 1.15, 4.77)] and MBL/MBP-C [1.6 (1.07, 2.42)] levels increased the odds of uncontrolled symptoms, whereas higher MK08/MAPK8 [0.48 (0.29, 0.76)] and CD5L [0.59 (0.41, 0.82)] levels decreased the odds. CD5L levels were significantly lower in severe asthma than in healthy controls [estimate -0.23 (95% CI -0.41, -0.04)]. No associations were found between symptom control and the sputum proteome (N = 90) or the sputum (N = 96) and blood (N = 360) transcriptomes.CONCLUSIONFour serum proteins distinguished asthmatics with uncontrolled from controlled symptoms. CD5L levels were also lower in asthmatics with severe disease than in healthy controls, warranting further investigation into its potential therapeutic value.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"135 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana M Gimenez-Arnau,Marcus Maurer,Adam Reich,Chia-Yu Chu,Diana Deleanu,Gordon Sussman,Jorge Sanchez,Knut Brockow,Koremasa Hayama,Michihiro Hide,Mohamed Denguezli,Raisa Meshkova,Roberta F J Criado,Sarbjit Saini,Solange Valle,Eva Hua,Pengpeng Wang,Alis Burciu,Isabelle Indermuehle,Vineeth Varanasi,Yolandi Joubert,Thomas Severin,Manmath Patekar
BACKGROUNDChronic spontaneous urticaria (CSU) is a debilitating skin condition affecting approximately 1% of the global population, characterized by recurrent wheals, angioedema, or both for over 6 weeks without identifiable external triggers.METHODSThis Phase 3b multicentre, double-blinded followed by open-label extension study evaluated the long-term efficacy and safety of ligelizumab re-treatment in patients with CSU who rolled over from previous studies. Patients from the PEARL-1 or PEARL-2 Phase 3 trials (re-treatment subpopulation) received blinded re-treatment with ligelizumab 72 mg or 120 mg every 4 weeks for 12 weeks, followed by open-label ligelizumab 120 mg up to Week 104. Patients from a Phase 3 open-label Japanese study or a Phase 2 pediatric study received open-label ligelizumab 120 mg throughout. Primary and key secondary efficacy endpoints were assessed at Week 12 in the re-treatment subpopulation; safety was evaluated throughout.RESULTSIn the overall ligelizumab re-treatment subpopulation, 53.5% and 57.5% of patients treated with ligelizumab 72 mg and 120 mg, respectively, achieved weekly urticaria activity score (UAS7) of ≤ 6 at Week 12. Re-treatment efficacy was demonstrated in both treatment arms, across all secondary endpoints, maintained up to Week 52. Re-treatment efficacy in the overall trial population showed similar trends to those in the re-treatment subpopulation. The safety profile of ligelizumab showed no new or unexpected safety signals compared with the known safety profile of ligelizumab.CONCLUSIONLong-term and re-treatment with ligelizumab was well tolerated and efficacious in patients with CSU, aligning with the short-term outcomes observed in the Phase 3 PEARL studies.
{"title":"Long-Term Efficacy and Safety of Ligelizumab as Re-Treatment in Patients With Chronic Spontaneous Urticaria.","authors":"Ana M Gimenez-Arnau,Marcus Maurer,Adam Reich,Chia-Yu Chu,Diana Deleanu,Gordon Sussman,Jorge Sanchez,Knut Brockow,Koremasa Hayama,Michihiro Hide,Mohamed Denguezli,Raisa Meshkova,Roberta F J Criado,Sarbjit Saini,Solange Valle,Eva Hua,Pengpeng Wang,Alis Burciu,Isabelle Indermuehle,Vineeth Varanasi,Yolandi Joubert,Thomas Severin,Manmath Patekar","doi":"10.1111/all.70181","DOIUrl":"https://doi.org/10.1111/all.70181","url":null,"abstract":"BACKGROUNDChronic spontaneous urticaria (CSU) is a debilitating skin condition affecting approximately 1% of the global population, characterized by recurrent wheals, angioedema, or both for over 6 weeks without identifiable external triggers.METHODSThis Phase 3b multicentre, double-blinded followed by open-label extension study evaluated the long-term efficacy and safety of ligelizumab re-treatment in patients with CSU who rolled over from previous studies. Patients from the PEARL-1 or PEARL-2 Phase 3 trials (re-treatment subpopulation) received blinded re-treatment with ligelizumab 72 mg or 120 mg every 4 weeks for 12 weeks, followed by open-label ligelizumab 120 mg up to Week 104. Patients from a Phase 3 open-label Japanese study or a Phase 2 pediatric study received open-label ligelizumab 120 mg throughout. Primary and key secondary efficacy endpoints were assessed at Week 12 in the re-treatment subpopulation; safety was evaluated throughout.RESULTSIn the overall ligelizumab re-treatment subpopulation, 53.5% and 57.5% of patients treated with ligelizumab 72 mg and 120 mg, respectively, achieved weekly urticaria activity score (UAS7) of ≤ 6 at Week 12. Re-treatment efficacy was demonstrated in both treatment arms, across all secondary endpoints, maintained up to Week 52. Re-treatment efficacy in the overall trial population showed similar trends to those in the re-treatment subpopulation. The safety profile of ligelizumab showed no new or unexpected safety signals compared with the known safety profile of ligelizumab.CONCLUSIONLong-term and re-treatment with ligelizumab was well tolerated and efficacious in patients with CSU, aligning with the short-term outcomes observed in the Phase 3 PEARL studies.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"242 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maurizio Margaglione, Maria D'Apolito, Rosa Santacroce, Giorgia Cordisco, Francesco Arcoleo, Tiziana De Pasquale, Ilaria Puxeddu, Andrea Zanichelli, Mauro Cancian
{"title":"Unveiling Rare Genetic Variants in DAB2IP : New Insights Into the Pathogenesis of Recurrent Angioedema","authors":"Maurizio Margaglione, Maria D'Apolito, Rosa Santacroce, Giorgia Cordisco, Francesco Arcoleo, Tiziana De Pasquale, Ilaria Puxeddu, Andrea Zanichelli, Mauro Cancian","doi":"10.1111/all.70184","DOIUrl":"https://doi.org/10.1111/all.70184","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"20 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rakesh Natarajan, Brooke Szczesny, Kanika Kanchan, Erika Esquinca, Meher Preethi Boorgula, Sameer Chavan, Monica Campbell, Wendy Lorizio, Ayo P. Doumatey, Alvaro A. Cruz, Harold Watson, Edward T. Naureckas, B. Louise Giles, Ganiyu Arinola, Olumide Sogaolu, Adegoke G. Falade, Nadia N. Hansel, Christopher O. Olopade, Charles N. Rotimi, R. Clive Landis, Camila A. Figueiredo, Eimear E. Kenny, Ingo Ruczinski, Andrew H. Liu, Carole Ober, Margaret A. Taub, Randi K. Johnson, Kathleen C. Barnes, Genevieve L. Wojcik, Rasika A. Mathias
Background Existing asthma polygenic risk scores (PRSs) have minimal validation in African‐ancestry populations, leaving gaps in our understanding of the wide applicability of PRSs. To widen our understanding of the applicability of asthma PRSs, we apply published PRSs in African‐ancestry individuals and quantify the extent to which the PRS‐asthma relationship is mediated by clinical biomarkers and gene‐expression signatures of asthma. Methods We applied 22 PRSs from the PGS Catalog in 673 individuals from the Consortium on Asthma among African‐Ancestry Populations in the Americas (CAAPA) and calculated the percent of the PRS‐asthma relationship that is statistically mediated by clinical and nasal epithelium transcriptomic biomarkers of asthma. Asthma case/control status was defined as ever/never having a doctor's diagnosis of disease. For gene expression mediation analysis, we limited the cases to those with current disease. Results The PRS (PGS001782) created by the Global Biobank Meta‐analysis Initiative ( N = 32,658 individuals of African ancestry) performed the best (ΔAUC = 0.104, AUC = 0.657) adjusted for age, sex, study site, and the first two genetic principal components (PC1‐2). The PRS's effect on asthma was mediated by total IgE (tIgE) (38.8%, p .adj < 0.0002), multi‐allergen ImmunoCAP phadiatop specific IgE (sIgE) (38.7%, p .adj < 0.0002), and eosinophils (7.3%, p .adj = 0.004). Mediation was observed for gene expression modules related to T2 inflammation (21.9%, p .adj < 0.0024), wound healing (11.9%, p .adj = 0.008), and medication response (6.8%, p .adj = 0.049). Conclusion We found the best PRS to be the one derived using the largest sample size and including African‐ancestry individuals. Mediation supports the well‐documented biology of T2 inflammation in asthma as well as pathophysiological components of asthma like wound healing and medication response.
{"title":"Mediation of Polygenic Asthma Risk Through Gene Expression","authors":"Rakesh Natarajan, Brooke Szczesny, Kanika Kanchan, Erika Esquinca, Meher Preethi Boorgula, Sameer Chavan, Monica Campbell, Wendy Lorizio, Ayo P. Doumatey, Alvaro A. Cruz, Harold Watson, Edward T. Naureckas, B. Louise Giles, Ganiyu Arinola, Olumide Sogaolu, Adegoke G. Falade, Nadia N. Hansel, Christopher O. Olopade, Charles N. Rotimi, R. Clive Landis, Camila A. Figueiredo, Eimear E. Kenny, Ingo Ruczinski, Andrew H. Liu, Carole Ober, Margaret A. Taub, Randi K. Johnson, Kathleen C. Barnes, Genevieve L. Wojcik, Rasika A. Mathias","doi":"10.1111/all.70101","DOIUrl":"https://doi.org/10.1111/all.70101","url":null,"abstract":"Background Existing asthma polygenic risk scores (PRSs) have minimal validation in African‐ancestry populations, leaving gaps in our understanding of the wide applicability of PRSs. To widen our understanding of the applicability of asthma PRSs, we apply published PRSs in African‐ancestry individuals and quantify the extent to which the PRS‐asthma relationship is mediated by clinical biomarkers and gene‐expression signatures of asthma. Methods We applied 22 PRSs from the PGS Catalog in 673 individuals from the Consortium on Asthma among African‐Ancestry Populations in the Americas (CAAPA) and calculated the percent of the PRS‐asthma relationship that is statistically mediated by clinical and nasal epithelium transcriptomic biomarkers of asthma. Asthma case/control status was defined as ever/never having a doctor's diagnosis of disease. For gene expression mediation analysis, we limited the cases to those with current disease. Results The PRS (PGS001782) created by the Global Biobank Meta‐analysis Initiative ( <jats:italic>N</jats:italic> = 32,658 individuals of African ancestry) performed the best (ΔAUC = 0.104, AUC = 0.657) adjusted for age, sex, study site, and the first two genetic principal components (PC1‐2). The PRS's effect on asthma was mediated by total IgE (tIgE) (38.8%, <jats:italic>p</jats:italic> .adj < 0.0002), multi‐allergen ImmunoCAP phadiatop specific IgE (sIgE) (38.7%, <jats:italic>p</jats:italic> .adj < 0.0002), and eosinophils (7.3%, <jats:italic>p</jats:italic> .adj = 0.004). Mediation was observed for gene expression modules related to T2 inflammation (21.9%, <jats:italic>p</jats:italic> .adj < 0.0024), wound healing (11.9%, <jats:italic>p</jats:italic> .adj = 0.008), and medication response (6.8%, <jats:italic>p</jats:italic> .adj = 0.049). Conclusion We found the best PRS to be the one derived using the largest sample size and including African‐ancestry individuals. Mediation supports the well‐documented biology of T2 inflammation in asthma as well as pathophysiological components of asthma like wound healing and medication response.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"141 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Between Healing and Harm: The Two Faces of Acetylcholine in Lung Immunity","authors":"Alessandra Ruiz‐Sánchez, Emilio Nuñez‐Borque, Rodrigo Jiménez‐Saiz","doi":"10.1111/all.70185","DOIUrl":"https://doi.org/10.1111/all.70185","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"56 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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