Diamant, Zuzana

Hanania, Nicola A

van den Berge, Maarten

English

University of Groningen

   University of GroningenEditorialDiamant, Zuzana; van den Berge, Maarten; Hanania, Nicola APublished in:Current Opinion in Pulmonary MedicineDOI:10.1097/MCP.0000000000000650IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2020Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Diamant, Z., van den Berge, M., & Hanania, N. A. (2020). Editorial: Asthma: a modifiable disease on acrossroad. Current Opinion in Pulmonary Medicine, 26(1), 1-2.https://doi.org/10.1097/MCP.0000000000000650CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 19-11-2022Downloadedfromhttps://journals.lww.com/co-pulmonarymedicinebyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3mH5nK33R3QitS123Wq8VstcFeB1oKb/CKMiJMDrOyyz0qtOsvBMVXg==on02/14/2020Downloadedfromhttps://journals.lww.com/co-pulmonarymedicinebyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3mH5nK33R3QitS123Wq8VstcFeB1oKb/CKMiJMDrOyyz0qtOsvBMVXg==on02/14/2020 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. CURRENTOPINION Asthma: a modifiable disease on a crossroadZuzana Diamanta,b,c, Maarten van den Berged, and Nicola A. HananiaeWhile asthma is an old disease, we have come a longway to better understanding this syndrome in the lastfew years. More recently, there has been a substantialincrease in our insights into the immunologicalmechanisms underlying the pathogenesis of asthmawhich helped define several phenotypes and endo-types [1]. Along with mapping of several endogenouspathways related to asthma which drive the develop-ment of targeted therapies, an increasing number ofboth external and internal factors inducing or mod-ulating these pathways have also been identified.Our better insight and understanding of ‘modifiable’factors of asthma will likely improve our approach toits management and thus lead to better outcomes inpatients struggling with this disease.In this issue, Sánchez-Garcı́a et al. [2], discuss thepotential risk factors of asthma from in-utero andmaternal exposures to infancy and childhood riskfactors and point out the role of few preventivestrategies that have been studied or need to be exam-ined. Bontinck et al. [3] report on the effects inducedby the exposome, represented by air pollutants, onhuman well being in general and, specifically, onairways and lung health. Air pollutants includingparticulate matter, NO2 and ozone which arise fromroad traffic, industries and other human pollutingactivities, trigger upper and lower airway inflamma-tionand, thus, can bothinduceandexacerbateairwaydiseases such as rhinitis and asthma. In close associa-tion with this topic, Steelant et al. [4] report on theepithelial dysfunction and its consequences onchronic respiratory diseases. Furthermore, interestingnew insights on both external and internal disease-modifying factors, that is the environmental and‘endogenous’ microbiome, are addressed by Kozikand Huang [5]. They discuss several recent findingsunderscoring the accumulating evidence that withindefined time-windows in life, microbiota have animportant (immune) modifying role in asthma path-ogenesis and in shaping the asthma phenotype. Inaddition, they address the interactions of both indoormicrobiome (or aerobiome) and ‘endogenous’ micro-biome with environmental factors (e.g. allergens,ozone, etc) and their effects on asthma.Apart from environmental factors, the clinicalexpression of asthma in individual patients is com-posed of multiple, partly overlapping, pathophysio-logical features and their underlying mechanisms. Toimplement precision medicine into daily practice,Agusti et al. [6] introduced the holistic concept oftreatable traits. The bottom line, this approach comesdown to proactive identification of all disease-relatedcomponents within individual patients that can betreated as part of a personalized management plan. Itthis issue, Ulrik et al. [7] provide an update on thetreatable traits topic, which is being extended to‘treatable mechanisms’ by uncovering underlyingmolecular pathways and identifying reliable bio-markers to further refine targeted treatments in indi-vidual patients. According to Pitzner-Fabricius et al.regular exercise can improve both symptoms andinflammation [8], while both pulmonary and extra-pulmonary comorbidities have a major impacton thecourse of asthma. Bahmer et al. [9] discuss the com-plexity of several aspects of airway remodeling, itschanges throughout the life-cycle and the urgentneed of adequate biomarkers to monitor treatmentrespons in clinical daily practice. Rogliani et al. [10]discuss the importance of accurately identifying andmanaging comorbidities especially in patients withuncontrolled disease.The identification of molecular pathways under-lying type 2 asthma has driven the development ofseveral targeted biologics and small molecules. Alar-mins [IL25, IL33 and thymic stromal lymphopoietin(TSLP)] act upstream in the inflammatory cascadethrough activation of dendritic cells and polarizingT cells to produce type 2 cytokines. In addition, theycan directly activate several effector cells that play aaDepartment of Respiratory Medicine & Allergology, Institute for ClinicalScience, Skane University Hospital, Lund University, Lund, Sweden,bDepartment of Respiratory Medicine, First Faculty of Medicine, CharlesUniversity and Thomayer Hospital, Prague, Czech Republic, cDepartmentof Clinical Pharmacy & Pharmacology, University Groningen, UniversityMedical Center Groningen and QPS-NL, dDepartment of RespiratoryMedicine, University Groningen, University Medical Center Groningen,Groningen, The Netherlands and eSection of Pulmonary and CareMedicine, Airways Clinical Research Center, Baylor College of Medicine,Houston, Texas, USACorrespondence to Prof. Zuzana Diamant, MD, PhD, Department ofClinical Pharmacy & Pharmacology, University Groningen, UniversityMedical Center Groningen and QPS-NL, Hanzeplein 1, Entrance 53,9713 AG Groningen, The Netherlands. Tel: +31 0 50 3048012;e-mail: z.diamant@gems.demon.nlCurr Opin Pulm Med 2020, 26:1–2DOI:10.1097/MCP.00000000000006501070-5287 Copyright  2019 Wolters Kluwer Health, Inc. All rights reserved. www.co-pulmonarymedicine.comEDITORIAL Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.central role in both allergic and nonallergic asthma.As discussed by van der Veen et al. [11], the asth-matic inflammatory process can be shifted towardseither a Th2 or a Th1 environment depending onspecific macrophage subtypes present within theairway wall. Gauvreau et al. [12] discuss the potentialof targeting TSLP in the treatment of type 2 asthma,while blocking IL33 and IL25 may help to definetheir respective role in (the treatment of) asthma. Inline with principles of precision medicine and theincreased emphasis on targeted therapies in patientswith severe asthma, Vijverberg et al. [13] discuss theurgent need of clinically reliable biomarkers to guidetargeted treatment options in pediatric patientswith severe disease. Christenson [14] discusses theuse of specific gene signatures representing path-ways like Th2 and IL17 to explore the presence ofsuch treatable mechanisms in individual patients.The development and clinical implementationof targeted drugs into the management of severeasthma allows for the reduction of the overall cor-ticosteroid load in this patient population. Slisz andVasakova [15] advocate a holistic personalizedapproach to asthma management, which – apartfrom pheno/endotyping – should also include theoverall (systemic) corticosteroid use with proactivedocumentation, prophylaxis and treatment ofcorticosteroid-related adverse events. Timely imple-mentation of the most appropriate targeted treat-ment options based on adequate biomarkers shouldbe part of the approach.In summary, our modern understanding of thepathophysiology, triggers and risk factors of asthmahave allowed us to ‘think differently’ about thisdisease. However, despite great progress in unravel-ling several molecular mechanisms underlying thepathogenesis of asthma and the development ofseveral effective targeted treatment options, severalquestions remain unanswered (Table 1). Ongoingand future clinical studies should address thesequestions with the hope that this will help to furthershape the precision medicine approach to asthma.AcknowledgementsNone.Financial support and sponsorshipNone.Conflicts of interestZ.D. has received honoraria for serving on advisoryboards or as a consultant with ALK, Aquilon, AstraZe-neca, Boehringer-Ingelheim, CSL-Behring, HAL-Allergy,MSD, Sanofi-Genzyme. Her institution has receivedresearch support from Foresee Pharmaceuticals, Novartisand Patara pharma.M.v.d.B. reports research grants paid to his institutionfrom GlaxoSmithKline, Chiesi, Astra Zeneca and TEVAPharma.N.A.H. has received honoraria for serving on advisoryboards or as consultant with GSK, Boehringer Ingelheim(BI), Novartis, Sanofi Genzyme, Regeneron, Astra Zenecaand Genentech. His institution has received researchsupport on his behalf from GSK, BI, Astra Zeneca,Novartis and Sanofi.REFERENCES1. Diamant Z, Vijverberg S, Alving K, et al. Towards clinically applicable biomarkersof asthma – an EAACI position paper. Allergy 2019; 74:1835–1851.2. Sánchez-Garcı́a S, Rial MJ, Domı́nguez-Ortega J. Long and winding road:from infant wheeze to adult asthma. Curr Opin Pulm Med 2020; 26:3–9.3. Bontinck A, Maes T, Joos G. Asthma and air pollution: recent insights inpathogenesis and clinical implications. Curr Opin Pulm Med 2020; 26:10–19.4. Steelant B. Epithelial dysfunction in chronic respiratory diseases, a sharedendotype? Curr Opin Pulm Med 2020; 26:20–26.5. Kozik A, Huang YJ. Ecological interactions in asthma: from environment tomicrobiota and immune responses. Curr Opin Pulm Med 2020; 26:27–32.6. Agusti A, Bel E, Thomas M, et al. Treatable traits: toward precision medicine ofchronic airway diseases. Eur Respir J 2016; 47:410–419.7. Ulrik CS, Vijverberg S, Hanania NA, Diamant Z. Precision medicine andtreatable traits in chronic airway diseases - where do we stand? Curr OpinPulm Med 2020; 26:33–39.8. Pitzner-Fabricius A, Toennesen L, Backer V. Can training induce inflammatorycontrol in asthma, or is it symptom control only? Curr Opin Pulm Med 2020;26:56–61.9. Bahmer T, B€ulow Sand JM, Weckmann M. Lost in transition: biomarkers ofremodeling in patients with asthma. Curr Opin Pulm Med 2020; 26:40–46.10. Rogliani P, Sforza M, Calzetta L. The impact of comorbidities on severeasthma. Curr Opin Pulm Med 2020; 26:47–55.11. van der Veen TA, de Groot LES, Melgert BN. The different faces of themacrophage in asthma. Curr Opin Pulm Med 2020; 26:62–68.12. Gauvreau GM, White L, Davis BE. Anti-alarmin approaches entering clinicaltrials. Curr Opin Pulm Med 2020; 26:69–76.13. Vijverberg SJH, Brinkman P, Rutjes NWP, Maitland-van der Zee AH. Precisionmedicine in severe pediatric asthma: opportunities and challenges. Curr OpinPulm Med 2020; 26:77–83.14. Christenson SA. The role of genomic profiling in identifying molecular phe-notypes in obstructive lung diseases. Curr Opin Pulm Med 2020; 26:84–89.15. Slisz T, Vasakova M. The burden of corticosteroid overload in severe anddifficult to treat asthma: how to reduce this? Curr Opin Pulm Med 2020;26:90–96.Table 1. Unanswered questions to be addressed for novel-targeted asthma therapies (biologics and small molecules)Which pathway should be (preferably) targeted (in the first place)by which biologic or SM in an individual patient with an‘overlapping’ phenotype/endotype?What is the optimal duration for a given therapy in an individualpatient?What are the stopping rules for an individual-targeted therapy?What is the long-term safety of biologics in the general asthmapopulation and selected special populations (e.g. children,pregnant and elderly patients)?What is the feasibility of administering a combination of biologicsand/or SM and will that improve the efficacy and maintainsafety of the therapies?Can chronic use of biologics and/or SM alter the natural course ofthe disease or come close to actually curing the disease?Can the use of biologics and/or SM in high-risk individualsprevent the onset of asthma?SM, small molecules.Asthma2 www.co-pulmonarymedicine.com Volume 26  Number 1  January 2020

Editorial:Asthma: a modifiable disease on a crossroad

   University of GroningenEditorialDiamant, Zuzana; van den Berge, Maarten; Hanania, Nicola APublished in:Current Opinion in Pulmonary MedicineDOI:10.1097/MCP.0000000000000650IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2020Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Diamant, Z., van den Berge, M., & Hanania, N. A. (2020). Editorial: Asthma: a modifiable disease on acrossroad. Current Opinion in Pulmonary Medicine, 26(1), 1-2.https://doi.org/10.1097/MCP.0000000000000650CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 29-04-2023Downloadedfromhttps://journals.lww.com/co-pulmonarymedicinebyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3mH5nK33R3QitS123Wq8VstcFeB1oKb/CKMiJMDrOyyz0qtOsvBMVXg==on02/14/2020Downloadedfromhttps://journals.lww.com/co-pulmonarymedicinebyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3mH5nK33R3QitS123Wq8VstcFeB1oKb/CKMiJMDrOyyz0qtOsvBMVXg==on02/14/2020 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. CURRENTOPINION Asthma: a modifiable disease on a crossroadZuzana Diamanta,b,c, Maarten van den Berged, and Nicola A. HananiaeWhile asthma is an old disease, we have come a longway to better understanding this syndrome in the lastfew years. More recently, there has been a substantialincrease in our insights into the immunologicalmechanisms underlying the pathogenesis of asthmawhich helped define several phenotypes and endo-types [1]. Along with mapping of several endogenouspathways related to asthma which drive the develop-ment of targeted therapies, an increasing number ofboth external and internal factors inducing or mod-ulating these pathways have also been identified.Our better insight and understanding of ‘modifiable’factors of asthma will likely improve our approach toits management and thus lead to better outcomes inpatients struggling with this disease.In this issue, Sánchez-Garcı́a et al. [2], discuss thepotential risk factors of asthma from in-utero andmaternal exposures to infancy and childhood riskfactors and point out the role of few preventivestrategies that have been studied or need to be exam-ined. Bontinck et al. [3] report on the effects inducedby the exposome, represented by air pollutants, onhuman well being in general and, specifically, onairways and lung health. Air pollutants includingparticulate matter, NO2 and ozone which arise fromroad traffic, industries and other human pollutingactivities, trigger upper and lower airway inflamma-tionand, thus, can bothinduceandexacerbateairwaydiseases such as rhinitis and asthma. In close associa-tion with this topic, Steelant et al. [4] report on theepithelial dysfunction and its consequences onchronic respiratory diseases. Furthermore, interestingnew insights on both external and internal disease-modifying factors, that is the environmental and‘endogenous’ microbiome, are addressed by Kozikand Huang [5]. They discuss several recent findingsunderscoring the accumulating evidence that withindefined time-windows in life, microbiota have animportant (immune) modifying role in asthma path-ogenesis and in shaping the asthma phenotype. Inaddition, they address the interactions of both indoormicrobiome (or aerobiome) and ‘endogenous’ micro-biome with environmental factors (e.g. allergens,ozone, etc) and their effects on asthma.Apart from environmental factors, the clinicalexpression of asthma in individual patients is com-posed of multiple, partly overlapping, pathophysio-logical features and their underlying mechanisms. Toimplement precision medicine into daily practice,Agusti et al. [6] introduced the holistic concept oftreatable traits. The bottom line, this approach comesdown to proactive identification of all disease-relatedcomponents within individual patients that can betreated as part of a personalized management plan. Itthis issue, Ulrik et al. [7] provide an update on thetreatable traits topic, which is being extended to‘treatable mechanisms’ by uncovering underlyingmolecular pathways and identifying reliable bio-markers to further refine targeted treatments in indi-vidual patients. According to Pitzner-Fabricius et al.regular exercise can improve both symptoms andinflammation [8], while both pulmonary and extra-pulmonary comorbidities have a major impacton thecourse of asthma. Bahmer et al. [9] discuss the com-plexity of several aspects of airway remodeling, itschanges throughout the life-cycle and the urgentneed of adequate biomarkers to monitor treatmentrespons in clinical daily practice. Rogliani et al. [10]discuss the importance of accurately identifying andmanaging comorbidities especially in patients withuncontrolled disease.The identification of molecular pathways under-lying type 2 asthma has driven the development ofseveral targeted biologics and small molecules. Alar-mins [IL25, IL33 and thymic stromal lymphopoietin(TSLP)] act upstream in the inflammatory cascadethrough activation of dendritic cells and polarizingT cells to produce type 2 cytokines. In addition, theycan directly activate several effector cells that play aaDepartment of Respiratory Medicine & Allergology, Institute for ClinicalScience, Skane University Hospital, Lund University, Lund, Sweden,bDepartment of Respiratory Medicine, First Faculty of Medicine, CharlesUniversity and Thomayer Hospital, Prague, Czech Republic, cDepartmentof Clinical Pharmacy & Pharmacology, University Groningen, UniversityMedical Center Groningen and QPS-NL, dDepartment of RespiratoryMedicine, University Groningen, University Medical Center Groningen,Groningen, The Netherlands and eSection of Pulmonary and CareMedicine, Airways Clinical Research Center, Baylor College of Medicine,Houston, Texas, USACorrespondence to Prof. Zuzana Diamant, MD, PhD, Department ofClinical Pharmacy & Pharmacology, University Groningen, UniversityMedical Center Groningen and QPS-NL, Hanzeplein 1, Entrance 53,9713 AG Groningen, The Netherlands. Tel: +31 0 50 3048012;e-mail: z.diamant@gems.demon.nlCurr Opin Pulm Med 2020, 26:1–2DOI:10.1097/MCP.00000000000006501070-5287 Copyright  2019 Wolters Kluwer Health, Inc. All rights reserved. www.co-pulmonarymedicine.comEDITORIAL Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.central role in both allergic and nonallergic asthma.As discussed by van der Veen et al. [11], the asth-matic inflammatory process can be shifted towardseither a Th2 or a Th1 environment depending onspecific macrophage subtypes present within theairway wall. Gauvreau et al. [12] discuss the potentialof targeting TSLP in the treatment of type 2 asthma,while blocking IL33 and IL25 may help to definetheir respective role in (the treatment of) asthma. Inline with principles of precision medicine and theincreased emphasis on targeted therapies in patientswith severe asthma, Vijverberg et al. [13] discuss theurgent need of clinically reliable biomarkers to guidetargeted treatment options in pediatric patientswith severe disease. Christenson [14] discusses theuse of specific gene signatures representing path-ways like Th2 and IL17 to explore the presence ofsuch treatable mechanisms in individual patients.The development and clinical implementationof targeted drugs into the management of severeasthma allows for the reduction of the overall cor-ticosteroid load in this patient population. Slisz andVasakova [15] advocate a holistic personalizedapproach to asthma management, which – apartfrom pheno/endotyping – should also include theoverall (systemic) corticosteroid use with proactivedocumentation, prophylaxis and treatment ofcorticosteroid-related adverse events. Timely imple-mentation of the most appropriate targeted treat-ment options based on adequate biomarkers shouldbe part of the approach.In summary, our modern understanding of thepathophysiology, triggers and risk factors of asthmahave allowed us to ‘think differently’ about thisdisease. However, despite great progress in unravel-ling several molecular mechanisms underlying thepathogenesis of asthma and the development ofseveral effective targeted treatment options, severalquestions remain unanswered (Table 1). Ongoingand future clinical studies should address thesequestions with the hope that this will help to furthershape the precision medicine approach to asthma.AcknowledgementsNone.Financial support and sponsorshipNone.Conflicts of interestZ.D. has received honoraria for serving on advisoryboards or as a consultant with ALK, Aquilon, AstraZe-neca, Boehringer-Ingelheim, CSL-Behring, HAL-Allergy,MSD, Sanofi-Genzyme. Her institution has receivedresearch support from Foresee Pharmaceuticals, Novartisand Patara pharma.M.v.d.B. reports research grants paid to his institutionfrom GlaxoSmithKline, Chiesi, Astra Zeneca and TEVAPharma.N.A.H. has received honoraria for serving on advisoryboards or as consultant with GSK, Boehringer Ingelheim(BI), Novartis, Sanofi Genzyme, Regeneron, Astra Zenecaand Genentech. His institution has received researchsupport on his behalf from GSK, BI, Astra Zeneca,Novartis and Sanofi.REFERENCES1. Diamant Z, Vijverberg S, Alving K, et al. Towards clinically applicable biomarkersof asthma – an EAACI position paper. Allergy 2019; 74:1835–1851.2. Sánchez-Garcı́a S, Rial MJ, Domı́nguez-Ortega J. Long and winding road:from infant wheeze to adult asthma. Curr Opin Pulm Med 2020; 26:3–9.3. Bontinck A, Maes T, Joos G. Asthma and air pollution: recent insights inpathogenesis and clinical implications. Curr Opin Pulm Med 2020; 26:10–19.4. Steelant B. Epithelial dysfunction in chronic respiratory diseases, a sharedendotype? Curr Opin Pulm Med 2020; 26:20–26.5. Kozik A, Huang YJ. Ecological interactions in asthma: from environment tomicrobiota and immune responses. Curr Opin Pulm Med 2020; 26:27–32.6. Agusti A, Bel E, Thomas M, et al. Treatable traits: toward precision medicine ofchronic airway diseases. Eur Respir J 2016; 47:410–419.7. Ulrik CS, Vijverberg S, Hanania NA, Diamant Z. Precision medicine andtreatable traits in chronic airway diseases - where do we stand? Curr OpinPulm Med 2020; 26:33–39.8. Pitzner-Fabricius A, Toennesen L, Backer V. Can training induce inflammatorycontrol in asthma, or is it symptom control only? Curr Opin Pulm Med 2020;26:56–61.9. Bahmer T, B€ulow Sand JM, Weckmann M. Lost in transition: biomarkers ofremodeling in patients with asthma. Curr Opin Pulm Med 2020; 26:40–46.10. Rogliani P, Sforza M, Calzetta L. The impact of comorbidities on severeasthma. Curr Opin Pulm Med 2020; 26:47–55.11. van der Veen TA, de Groot LES, Melgert BN. The different faces of themacrophage in asthma. Curr Opin Pulm Med 2020; 26:62–68.12. Gauvreau GM, White L, Davis BE. Anti-alarmin approaches entering clinicaltrials. Curr Opin Pulm Med 2020; 26:69–76.13. Vijverberg SJH, Brinkman P, Rutjes NWP, Maitland-van der Zee AH. Precisionmedicine in severe pediatric asthma: opportunities and challenges. Curr OpinPulm Med 2020; 26:77–83.14. Christenson SA. The role of genomic profiling in identifying molecular phe-notypes in obstructive lung diseases. Curr Opin Pulm Med 2020; 26:84–89.15. Slisz T, Vasakova M. The burden of corticosteroid overload in severe anddifficult to treat asthma: how to reduce this? Curr Opin Pulm Med 2020;26:90–96.Table 1. Unanswered questions to be addressed for novel-targeted asthma therapies (biologics and small molecules)Which pathway should be (preferably) targeted (in the first place)by which biologic or SM in an individual patient with an‘overlapping’ phenotype/endotype?What is the optimal duration for a given therapy in an individualpatient?What are the stopping rules for an individual-targeted therapy?What is the long-term safety of biologics in the general asthmapopulation and selected special populations (e.g. children,pregnant and elderly patients)?What is the feasibility of administering a combination of biologicsand/or SM and will that improve the efficacy and maintainsafety of the therapies?Can chronic use of biologics and/or SM alter the natural course ofthe disease or come close to actually curing the disease?Can the use of biologics and/or SM in high-risk individualsprevent the onset of asthma?SM, small molecules.Asthma2 www.co-pulmonarymedicine.com Volume 26  Number 1  January 2020

ARTS repository - University of Groningen

   University of GroningenEditorialDiamant, Zuzana; van den Berge, Maarten; Hanania, Nicola APublished in:Current Opinion in Pulmonary MedicineDOI:10.1097/MCP.0000000000000650IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2020Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Diamant, Z., van den Berge, M., & Hanania, N. A. (2020). Editorial: Asthma: a modifiable disease on acrossroad. Current Opinion in Pulmonary Medicine, 26(1), 1-2.https://doi.org/10.1097/MCP.0000000000000650CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 01-11-2023Downloadedfromhttps://journals.lww.com/co-pulmonarymedicinebyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3mH5nK33R3QitS123Wq8VstcFeB1oKb/CKMiJMDrOyyz0qtOsvBMVXg==on02/14/2020Downloadedfromhttps://journals.lww.com/co-pulmonarymedicinebyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3mH5nK33R3QitS123Wq8VstcFeB1oKb/CKMiJMDrOyyz0qtOsvBMVXg==on02/14/2020 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. CURRENTOPINION Asthma: a modifiable disease on a crossroadZuzana Diamanta,b,c, Maarten van den Berged, and Nicola A. HananiaeWhile asthma is an old disease, we have come a longway to better understanding this syndrome in the lastfew years. More recently, there has been a substantialincrease in our insights into the immunologicalmechanisms underlying the pathogenesis of asthmawhich helped define several phenotypes and endo-types [1]. Along with mapping of several endogenouspathways related to asthma which drive the develop-ment of targeted therapies, an increasing number ofboth external and internal factors inducing or mod-ulating these pathways have also been identified.Our better insight and understanding of ‘modifiable’factors of asthma will likely improve our approach toits management and thus lead to better outcomes inpatients struggling with this disease.In this issue, Sánchez-Garcı́a et al. [2], discuss thepotential risk factors of asthma from in-utero andmaternal exposures to infancy and childhood riskfactors and point out the role of few preventivestrategies that have been studied or need to be exam-ined. Bontinck et al. [3] report on the effects inducedby the exposome, represented by air pollutants, onhuman well being in general and, specifically, onairways and lung health. Air pollutants includingparticulate matter, NO2 and ozone which arise fromroad traffic, industries and other human pollutingactivities, trigger upper and lower airway inflamma-tionand, thus, can bothinduceandexacerbateairwaydiseases such as rhinitis and asthma. In close associa-tion with this topic, Steelant et al. [4] report on theepithelial dysfunction and its consequences onchronic respiratory diseases. Furthermore, interestingnew insights on both external and internal disease-modifying factors, that is the environmental and‘endogenous’ microbiome, are addressed by Kozikand Huang [5]. They discuss several recent findingsunderscoring the accumulating evidence that withindefined time-windows in life, microbiota have animportant (immune) modifying role in asthma path-ogenesis and in shaping the asthma phenotype. Inaddition, they address the interactions of both indoormicrobiome (or aerobiome) and ‘endogenous’ micro-biome with environmental factors (e.g. allergens,ozone, etc) and their effects on asthma.Apart from environmental factors, the clinicalexpression of asthma in individual patients is com-posed of multiple, partly overlapping, pathophysio-logical features and their underlying mechanisms. Toimplement precision medicine into daily practice,Agusti et al. [6] introduced the holistic concept oftreatable traits. The bottom line, this approach comesdown to proactive identification of all disease-relatedcomponents within individual patients that can betreated as part of a personalized management plan. Itthis issue, Ulrik et al. [7] provide an update on thetreatable traits topic, which is being extended to‘treatable mechanisms’ by uncovering underlyingmolecular pathways and identifying reliable bio-markers to further refine targeted treatments in indi-vidual patients. According to Pitzner-Fabricius et al.regular exercise can improve both symptoms andinflammation [8], while both pulmonary and extra-pulmonary comorbidities have a major impacton thecourse of asthma. Bahmer et al. [9] discuss the com-plexity of several aspects of airway remodeling, itschanges throughout the life-cycle and the urgentneed of adequate biomarkers to monitor treatmentrespons in clinical daily practice. Rogliani et al. [10]discuss the importance of accurately identifying andmanaging comorbidities especially in patients withuncontrolled disease.The identification of molecular pathways under-lying type 2 asthma has driven the development ofseveral targeted biologics and small molecules. Alar-mins [IL25, IL33 and thymic stromal lymphopoietin(TSLP)] act upstream in the inflammatory cascadethrough activation of dendritic cells and polarizingT cells to produce type 2 cytokines. In addition, theycan directly activate several effector cells that play aaDepartment of Respiratory Medicine & Allergology, Institute for ClinicalScience, Skane University Hospital, Lund University, Lund, Sweden,bDepartment of Respiratory Medicine, First Faculty of Medicine, CharlesUniversity and Thomayer Hospital, Prague, Czech Republic, cDepartmentof Clinical Pharmacy & Pharmacology, University Groningen, UniversityMedical Center Groningen and QPS-NL, dDepartment of RespiratoryMedicine, University Groningen, University Medical Center Groningen,Groningen, The Netherlands and eSection of Pulmonary and CareMedicine, Airways Clinical Research Center, Baylor College of Medicine,Houston, Texas, USACorrespondence to Prof. Zuzana Diamant, MD, PhD, Department ofClinical Pharmacy & Pharmacology, University Groningen, UniversityMedical Center Groningen and QPS-NL, Hanzeplein 1, Entrance 53,9713 AG Groningen, The Netherlands. Tel: +31 0 50 3048012;e-mail: z.diamant@gems.demon.nlCurr Opin Pulm Med 2020, 26:1–2DOI:10.1097/MCP.00000000000006501070-5287 Copyright  2019 Wolters Kluwer Health, Inc. All rights reserved. www.co-pulmonarymedicine.comEDITORIAL Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.central role in both allergic and nonallergic asthma.As discussed by van der Veen et al. [11], the asth-matic inflammatory process can be shifted towardseither a Th2 or a Th1 environment depending onspecific macrophage subtypes present within theairway wall. Gauvreau et al. [12] discuss the potentialof targeting TSLP in the treatment of type 2 asthma,while blocking IL33 and IL25 may help to definetheir respective role in (the treatment of) asthma. Inline with principles of precision medicine and theincreased emphasis on targeted therapies in patientswith severe asthma, Vijverberg et al. [13] discuss theurgent need of clinically reliable biomarkers to guidetargeted treatment options in pediatric patientswith severe disease. Christenson [14] discusses theuse of specific gene signatures representing path-ways like Th2 and IL17 to explore the presence ofsuch treatable mechanisms in individual patients.The development and clinical implementationof targeted drugs into the management of severeasthma allows for the reduction of the overall cor-ticosteroid load in this patient population. Slisz andVasakova [15] advocate a holistic personalizedapproach to asthma management, which – apartfrom pheno/endotyping – should also include theoverall (systemic) corticosteroid use with proactivedocumentation, prophylaxis and treatment ofcorticosteroid-related adverse events. Timely imple-mentation of the most appropriate targeted treat-ment options based on adequate biomarkers shouldbe part of the approach.In summary, our modern understanding of thepathophysiology, triggers and risk factors of asthmahave allowed us to ‘think differently’ about thisdisease. However, despite great progress in unravel-ling several molecular mechanisms underlying thepathogenesis of asthma and the development ofseveral effective targeted treatment options, severalquestions remain unanswered (Table 1). Ongoingand future clinical studies should address thesequestions with the hope that this will help to furthershape the precision medicine approach to asthma.AcknowledgementsNone.Financial support and sponsorshipNone.Conflicts of interestZ.D. has received honoraria for serving on advisoryboards or as a consultant with ALK, Aquilon, AstraZe-neca, Boehringer-Ingelheim, CSL-Behring, HAL-Allergy,MSD, Sanofi-Genzyme. Her institution has receivedresearch support from Foresee Pharmaceuticals, Novartisand Patara pharma.M.v.d.B. reports research grants paid to his institutionfrom GlaxoSmithKline, Chiesi, Astra Zeneca and TEVAPharma.N.A.H. has received honoraria for serving on advisoryboards or as consultant with GSK, Boehringer Ingelheim(BI), Novartis, Sanofi Genzyme, Regeneron, Astra Zenecaand Genentech. His institution has received researchsupport on his behalf from GSK, BI, Astra Zeneca,Novartis and Sanofi.REFERENCES1. Diamant Z, Vijverberg S, Alving K, et al. Towards clinically applicable biomarkersof asthma – an EAACI position paper. Allergy 2019; 74:1835–1851.2. Sánchez-Garcı́a S, Rial MJ, Domı́nguez-Ortega J. Long and winding road:from infant wheeze to adult asthma. Curr Opin Pulm Med 2020; 26:3–9.3. Bontinck A, Maes T, Joos G. Asthma and air pollution: recent insights inpathogenesis and clinical implications. Curr Opin Pulm Med 2020; 26:10–19.4. Steelant B. Epithelial dysfunction in chronic respiratory diseases, a sharedendotype? Curr Opin Pulm Med 2020; 26:20–26.5. Kozik A, Huang YJ. Ecological interactions in asthma: from environment tomicrobiota and immune responses. Curr Opin Pulm Med 2020; 26:27–32.6. Agusti A, Bel E, Thomas M, et al. Treatable traits: toward precision medicine ofchronic airway diseases. Eur Respir J 2016; 47:410–419.7. Ulrik CS, Vijverberg S, Hanania NA, Diamant Z. Precision medicine andtreatable traits in chronic airway diseases - where do we stand? Curr OpinPulm Med 2020; 26:33–39.8. Pitzner-Fabricius A, Toennesen L, Backer V. Can training induce inflammatorycontrol in asthma, or is it symptom control only? Curr Opin Pulm Med 2020;26:56–61.9. Bahmer T, B€ulow Sand JM, Weckmann M. Lost in transition: biomarkers ofremodeling in patients with asthma. Curr Opin Pulm Med 2020; 26:40–46.10. Rogliani P, Sforza M, Calzetta L. The impact of comorbidities on severeasthma. Curr Opin Pulm Med 2020; 26:47–55.11. van der Veen TA, de Groot LES, Melgert BN. The different faces of themacrophage in asthma. Curr Opin Pulm Med 2020; 26:62–68.12. Gauvreau GM, White L, Davis BE. Anti-alarmin approaches entering clinicaltrials. Curr Opin Pulm Med 2020; 26:69–76.13. Vijverberg SJH, Brinkman P, Rutjes NWP, Maitland-van der Zee AH. Precisionmedicine in severe pediatric asthma: opportunities and challenges. Curr OpinPulm Med 2020; 26:77–83.14. Christenson SA. The role of genomic profiling in identifying molecular phe-notypes in obstructive lung diseases. Curr Opin Pulm Med 2020; 26:84–89.15. Slisz T, Vasakova M. The burden of corticosteroid overload in severe anddifficult to treat asthma: how to reduce this? Curr Opin Pulm Med 2020;26:90–96.Table 1. Unanswered questions to be addressed for novel-targeted asthma therapies (biologics and small molecules)Which pathway should be (preferably) targeted (in the first place)by which biologic or SM in an individual patient with an‘overlapping’ phenotype/endotype?What is the optimal duration for a given therapy in an individualpatient?What are the stopping rules for an individual-targeted therapy?What is the long-term safety of biologics in the general asthmapopulation and selected special populations (e.g. children,pregnant and elderly patients)?What is the feasibility of administering a combination of biologicsand/or SM and will that improve the efficacy and maintainsafety of the therapies?Can chronic use of biologics and/or SM alter the natural course ofthe disease or come close to actually curing the disease?Can the use of biologics and/or SM in high-risk individualsprevent the onset of asthma?SM, small molecules.Asthma2 www.co-pulmonarymedicine.com Volume 26  Number 1  January 2020

Hanania, Nicola A.

Lund University Publications

Editorial : Asthma: a modifiable disease on a crossroad

Dissertations of the University of Groningen

   University of GroningenEditorialDiamant, Zuzana; van den Berge, Maarten; Hanania, Nicola APublished in:Current Opinion in Pulmonary MedicineDOI:10.1097/MCP.0000000000000650IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2020Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Diamant, Z., van den Berge, M., & Hanania, N. A. (2020). Editorial: Asthma: a modifiable disease on acrossroad. Current Opinion in Pulmonary Medicine, 26(1), 1-2.https://doi.org/10.1097/MCP.0000000000000650CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 10-09-2023Downloadedfromhttps://journals.lww.com/co-pulmonarymedicinebyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3mH5nK33R3QitS123Wq8VstcFeB1oKb/CKMiJMDrOyyz0qtOsvBMVXg==on02/14/2020Downloadedfromhttps://journals.lww.com/co-pulmonarymedicinebyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3mH5nK33R3QitS123Wq8VstcFeB1oKb/CKMiJMDrOyyz0qtOsvBMVXg==on02/14/2020 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. CURRENTOPINION Asthma: a modifiable disease on a crossroadZuzana Diamanta,b,c, Maarten van den Berged, and Nicola A. HananiaeWhile asthma is an old disease, we have come a longway to better understanding this syndrome in the lastfew years. More recently, there has been a substantialincrease in our insights into the immunologicalmechanisms underlying the pathogenesis of asthmawhich helped define several phenotypes and endo-types [1]. Along with mapping of several endogenouspathways related to asthma which drive the develop-ment of targeted therapies, an increasing number ofboth external and internal factors inducing or mod-ulating these pathways have also been identified.Our better insight and understanding of ‘modifiable’factors of asthma will likely improve our approach toits management and thus lead to better outcomes inpatients struggling with this disease.In this issue, Sánchez-Garcı́a et al. [2], discuss thepotential risk factors of asthma from in-utero andmaternal exposures to infancy and childhood riskfactors and point out the role of few preventivestrategies that have been studied or need to be exam-ined. Bontinck et al. [3] report on the effects inducedby the exposome, represented by air pollutants, onhuman well being in general and, specifically, onairways and lung health. Air pollutants includingparticulate matter, NO2 and ozone which arise fromroad traffic, industries and other human pollutingactivities, trigger upper and lower airway inflamma-tionand, thus, can bothinduceandexacerbateairwaydiseases such as rhinitis and asthma. In close associa-tion with this topic, Steelant et al. [4] report on theepithelial dysfunction and its consequences onchronic respiratory diseases. Furthermore, interestingnew insights on both external and internal disease-modifying factors, that is the environmental and‘endogenous’ microbiome, are addressed by Kozikand Huang [5]. They discuss several recent findingsunderscoring the accumulating evidence that withindefined time-windows in life, microbiota have animportant (immune) modifying role in asthma path-ogenesis and in shaping the asthma phenotype. Inaddition, they address the interactions of both indoormicrobiome (or aerobiome) and ‘endogenous’ micro-biome with environmental factors (e.g. allergens,ozone, etc) and their effects on asthma.Apart from environmental factors, the clinicalexpression of asthma in individual patients is com-posed of multiple, partly overlapping, pathophysio-logical features and their underlying mechanisms. Toimplement precision medicine into daily practice,Agusti et al. [6] introduced the holistic concept oftreatable traits. The bottom line, this approach comesdown to proactive identification of all disease-relatedcomponents within individual patients that can betreated as part of a personalized management plan. Itthis issue, Ulrik et al. [7] provide an update on thetreatable traits topic, which is being extended to‘treatable mechanisms’ by uncovering underlyingmolecular pathways and identifying reliable bio-markers to further refine targeted treatments in indi-vidual patients. According to Pitzner-Fabricius et al.regular exercise can improve both symptoms andinflammation [8], while both pulmonary and extra-pulmonary comorbidities have a major impacton thecourse of asthma. Bahmer et al. [9] discuss the com-plexity of several aspects of airway remodeling, itschanges throughout the life-cycle and the urgentneed of adequate biomarkers to monitor treatmentrespons in clinical daily practice. Rogliani et al. [10]discuss the importance of accurately identifying andmanaging comorbidities especially in patients withuncontrolled disease.The identification of molecular pathways under-lying type 2 asthma has driven the development ofseveral targeted biologics and small molecules. Alar-mins [IL25, IL33 and thymic stromal lymphopoietin(TSLP)] act upstream in the inflammatory cascadethrough activation of dendritic cells and polarizingT cells to produce type 2 cytokines. In addition, theycan directly activate several effector cells that play aaDepartment of Respiratory Medicine & Allergology, Institute for ClinicalScience, Skane University Hospital, Lund University, Lund, Sweden,bDepartment of Respiratory Medicine, First Faculty of Medicine, CharlesUniversity and Thomayer Hospital, Prague, Czech Republic, cDepartmentof Clinical Pharmacy & Pharmacology, University Groningen, UniversityMedical Center Groningen and QPS-NL, dDepartment of RespiratoryMedicine, University Groningen, University Medical Center Groningen,Groningen, The Netherlands and eSection of Pulmonary and CareMedicine, Airways Clinical Research Center, Baylor College of Medicine,Houston, Texas, USACorrespondence to Prof. Zuzana Diamant, MD, PhD, Department ofClinical Pharmacy & Pharmacology, University Groningen, UniversityMedical Center Groningen and QPS-NL, Hanzeplein 1, Entrance 53,9713 AG Groningen, The Netherlands. Tel: +31 0 50 3048012;e-mail: z.diamant@gems.demon.nlCurr Opin Pulm Med 2020, 26:1–2DOI:10.1097/MCP.00000000000006501070-5287 Copyright  2019 Wolters Kluwer Health, Inc. All rights reserved. www.co-pulmonarymedicine.comEDITORIAL Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.central role in both allergic and nonallergic asthma.As discussed by van der Veen et al. [11], the asth-matic inflammatory process can be shifted towardseither a Th2 or a Th1 environment depending onspecific macrophage subtypes present within theairway wall. Gauvreau et al. [12] discuss the potentialof targeting TSLP in the treatment of type 2 asthma,while blocking IL33 and IL25 may help to definetheir respective role in (the treatment of) asthma. Inline with principles of precision medicine and theincreased emphasis on targeted therapies in patientswith severe asthma, Vijverberg et al. [13] discuss theurgent need of clinically reliable biomarkers to guidetargeted treatment options in pediatric patientswith severe disease. Christenson [14] discusses theuse of specific gene signatures representing path-ways like Th2 and IL17 to explore the presence ofsuch treatable mechanisms in individual patients.The development and clinical implementationof targeted drugs into the management of severeasthma allows for the reduction of the overall cor-ticosteroid load in this patient population. Slisz andVasakova [15] advocate a holistic personalizedapproach to asthma management, which – apartfrom pheno/endotyping – should also include theoverall (systemic) corticosteroid use with proactivedocumentation, prophylaxis and treatment ofcorticosteroid-related adverse events. Timely imple-mentation of the most appropriate targeted treat-ment options based on adequate biomarkers shouldbe part of the approach.In summary, our modern understanding of thepathophysiology, triggers and risk factors of asthmahave allowed us to ‘think differently’ about thisdisease. However, despite great progress in unravel-ling several molecular mechanisms underlying thepathogenesis of asthma and the development ofseveral effective targeted treatment options, severalquestions remain unanswered (Table 1). Ongoingand future clinical studies should address thesequestions with the hope that this will help to furthershape the precision medicine approach to asthma.AcknowledgementsNone.Financial support and sponsorshipNone.Conflicts of interestZ.D. has received honoraria for serving on advisoryboards or as a consultant with ALK, Aquilon, AstraZe-neca, Boehringer-Ingelheim, CSL-Behring, HAL-Allergy,MSD, Sanofi-Genzyme. Her institution has receivedresearch support from Foresee Pharmaceuticals, Novartisand Patara pharma.M.v.d.B. reports research grants paid to his institutionfrom GlaxoSmithKline, Chiesi, Astra Zeneca and TEVAPharma.N.A.H. has received honoraria for serving on advisoryboards or as consultant with GSK, Boehringer Ingelheim(BI), Novartis, Sanofi Genzyme, Regeneron, Astra Zenecaand Genentech. His institution has received researchsupport on his behalf from GSK, BI, Astra Zeneca,Novartis and Sanofi.REFERENCES1. Diamant Z, Vijverberg S, Alving K, et al. Towards clinically applicable biomarkersof asthma – an EAACI position paper. Allergy 2019; 74:1835–1851.2. Sánchez-Garcı́a S, Rial MJ, Domı́nguez-Ortega J. Long and winding road:from infant wheeze to adult asthma. Curr Opin Pulm Med 2020; 26:3–9.3. Bontinck A, Maes T, Joos G. Asthma and air pollution: recent insights inpathogenesis and clinical implications. Curr Opin Pulm Med 2020; 26:10–19.4. Steelant B. Epithelial dysfunction in chronic respiratory diseases, a sharedendotype? Curr Opin Pulm Med 2020; 26:20–26.5. Kozik A, Huang YJ. Ecological interactions in asthma: from environment tomicrobiota and immune responses. Curr Opin Pulm Med 2020; 26:27–32.6. Agusti A, Bel E, Thomas M, et al. Treatable traits: toward precision medicine ofchronic airway diseases. Eur Respir J 2016; 47:410–419.7. Ulrik CS, Vijverberg S, Hanania NA, Diamant Z. Precision medicine andtreatable traits in chronic airway diseases - where do we stand? Curr OpinPulm Med 2020; 26:33–39.8. Pitzner-Fabricius A, Toennesen L, Backer V. Can training induce inflammatorycontrol in asthma, or is it symptom control only? Curr Opin Pulm Med 2020;26:56–61.9. Bahmer T, B€ulow Sand JM, Weckmann M. Lost in transition: biomarkers ofremodeling in patients with asthma. Curr Opin Pulm Med 2020; 26:40–46.10. Rogliani P, Sforza M, Calzetta L. The impact of comorbidities on severeasthma. Curr Opin Pulm Med 2020; 26:47–55.11. van der Veen TA, de Groot LES, Melgert BN. The different faces of themacrophage in asthma. Curr Opin Pulm Med 2020; 26:62–68.12. Gauvreau GM, White L, Davis BE. Anti-alarmin approaches entering clinicaltrials. Curr Opin Pulm Med 2020; 26:69–76.13. Vijverberg SJH, Brinkman P, Rutjes NWP, Maitland-van der Zee AH. Precisionmedicine in severe pediatric asthma: opportunities and challenges. Curr OpinPulm Med 2020; 26:77–83.14. Christenson SA. The role of genomic profiling in identifying molecular phe-notypes in obstructive lung diseases. Curr Opin Pulm Med 2020; 26:84–89.15. Slisz T, Vasakova M. The burden of corticosteroid overload in severe anddifficult to treat asthma: how to reduce this? Curr Opin Pulm Med 2020;26:90–96.Table 1. Unanswered questions to be addressed for novel-targeted asthma therapies (biologics and small molecules)Which pathway should be (preferably) targeted (in the first place)by which biologic or SM in an individual patient with an‘overlapping’ phenotype/endotype?What is the optimal duration for a given therapy in an individualpatient?What are the stopping rules for an individual-targeted therapy?What is the long-term safety of biologics in the general asthmapopulation and selected special populations (e.g. children,pregnant and elderly patients)?What is the feasibility of administering a combination of biologicsand/or SM and will that improve the efficacy and maintainsafety of the therapies?Can chronic use of biologics and/or SM alter the natural course ofthe disease or come close to actually curing the disease?Can the use of biologics and/or SM in high-risk individualsprevent the onset of asthma?SM, small molecules.Asthma2 www.co-pulmonarymedicine.com Volume 26  Number 1  January 2020

Proceedings - University of Groningen

   University of GroningenEditorialDiamant, Zuzana; van den Berge, Maarten; Hanania, Nicola APublished in:Current Opinion in Pulmonary MedicineDOI:10.1097/MCP.0000000000000650IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2020Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Diamant, Z., van den Berge, M., & Hanania, N. A. (2020). Editorial: Asthma: a modifiable disease on acrossroad. Current Opinion in Pulmonary Medicine, 26(1), 1-2.https://doi.org/10.1097/MCP.0000000000000650CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 05-06-2022Downloadedfromhttps://journals.lww.com/co-pulmonarymedicinebyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3mH5nK33R3QitS123Wq8VstcFeB1oKb/CKMiJMDrOyyz0qtOsvBMVXg==on02/14/2020Downloadedfromhttps://journals.lww.com/co-pulmonarymedicinebyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3mH5nK33R3QitS123Wq8VstcFeB1oKb/CKMiJMDrOyyz0qtOsvBMVXg==on02/14/2020 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. CURRENTOPINION Asthma: a modifiable disease on a crossroadZuzana Diamanta,b,c, Maarten van den Berged, and Nicola A. HananiaeWhile asthma is an old disease, we have come a longway to better understanding this syndrome in the lastfew years. More recently, there has been a substantialincrease in our insights into the immunologicalmechanisms underlying the pathogenesis of asthmawhich helped define several phenotypes and endo-types [1]. Along with mapping of several endogenouspathways related to asthma which drive the develop-ment of targeted therapies, an increasing number ofboth external and internal factors inducing or mod-ulating these pathways have also been identified.Our better insight and understanding of ‘modifiable’factors of asthma will likely improve our approach toits management and thus lead to better outcomes inpatients struggling with this disease.In this issue, Sánchez-Garcı́a et al. [2], discuss thepotential risk factors of asthma from in-utero andmaternal exposures to infancy and childhood riskfactors and point out the role of few preventivestrategies that have been studied or need to be exam-ined. Bontinck et al. [3] report on the effects inducedby the exposome, represented by air pollutants, onhuman well being in general and, specifically, onairways and lung health. Air pollutants includingparticulate matter, NO2 and ozone which arise fromroad traffic, industries and other human pollutingactivities, trigger upper and lower airway inflamma-tionand, thus, can bothinduceandexacerbateairwaydiseases such as rhinitis and asthma. In close associa-tion with this topic, Steelant et al. [4] report on theepithelial dysfunction and its consequences onchronic respiratory diseases. Furthermore, interestingnew insights on both external and internal disease-modifying factors, that is the environmental and‘endogenous’ microbiome, are addressed by Kozikand Huang [5]. They discuss several recent findingsunderscoring the accumulating evidence that withindefined time-windows in life, microbiota have animportant (immune) modifying role in asthma path-ogenesis and in shaping the asthma phenotype. Inaddition, they address the interactions of both indoormicrobiome (or aerobiome) and ‘endogenous’ micro-biome with environmental factors (e.g. allergens,ozone, etc) and their effects on asthma.Apart from environmental factors, the clinicalexpression of asthma in individual patients is com-posed of multiple, partly overlapping, pathophysio-logical features and their underlying mechanisms. Toimplement precision medicine into daily practice,Agusti et al. [6] introduced the holistic concept oftreatable traits. The bottom line, this approach comesdown to proactive identification of all disease-relatedcomponents within individual patients that can betreated as part of a personalized management plan. Itthis issue, Ulrik et al. [7] provide an update on thetreatable traits topic, which is being extended to‘treatable mechanisms’ by uncovering underlyingmolecular pathways and identifying reliable bio-markers to further refine targeted treatments in indi-vidual patients. According to Pitzner-Fabricius et al.regular exercise can improve both symptoms andinflammation [8], while both pulmonary and extra-pulmonary comorbidities have a major impacton thecourse of asthma. Bahmer et al. [9] discuss the com-plexity of several aspects of airway remodeling, itschanges throughout the life-cycle and the urgentneed of adequate biomarkers to monitor treatmentrespons in clinical daily practice. Rogliani et al. [10]discuss the importance of accurately identifying andmanaging comorbidities especially in patients withuncontrolled disease.The identification of molecular pathways under-lying type 2 asthma has driven the development ofseveral targeted biologics and small molecules. Alar-mins [IL25, IL33 and thymic stromal lymphopoietin(TSLP)] act upstream in the inflammatory cascadethrough activation of dendritic cells and polarizingT cells to produce type 2 cytokines. In addition, theycan directly activate several effector cells that play aaDepartment of Respiratory Medicine & Allergology, Institute for ClinicalScience, Skane University Hospital, Lund University, Lund, Sweden,bDepartment of Respiratory Medicine, First Faculty of Medicine, CharlesUniversity and Thomayer Hospital, Prague, Czech Republic, cDepartmentof Clinical Pharmacy & Pharmacology, University Groningen, UniversityMedical Center Groningen and QPS-NL, dDepartment of RespiratoryMedicine, University Groningen, University Medical Center Groningen,Groningen, The Netherlands and eSection of Pulmonary and CareMedicine, Airways Clinical Research Center, Baylor College of Medicine,Houston, Texas, USACorrespondence to Prof. Zuzana Diamant, MD, PhD, Department ofClinical Pharmacy & Pharmacology, University Groningen, UniversityMedical Center Groningen and QPS-NL, Hanzeplein 1, Entrance 53,9713 AG Groningen, The Netherlands. Tel: +31 0 50 3048012;e-mail: z.diamant@gems.demon.nlCurr Opin Pulm Med 2020, 26:1–2DOI:10.1097/MCP.00000000000006501070-5287 Copyright  2019 Wolters Kluwer Health, Inc. All rights reserved. www.co-pulmonarymedicine.comEDITORIAL Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.central role in both allergic and nonallergic asthma.As discussed by van der Veen et al. [11], the asth-matic inflammatory process can be shifted towardseither a Th2 or a Th1 environment depending onspecific macrophage subtypes present within theairway wall. Gauvreau et al. [12] discuss the potentialof targeting TSLP in the treatment of type 2 asthma,while blocking IL33 and IL25 may help to definetheir respective role in (the treatment of) asthma. Inline with principles of precision medicine and theincreased emphasis on targeted therapies in patientswith severe asthma, Vijverberg et al. [13] discuss theurgent need of clinically reliable biomarkers to guidetargeted treatment options in pediatric patientswith severe disease. Christenson [14] discusses theuse of specific gene signatures representing path-ways like Th2 and IL17 to explore the presence ofsuch treatable mechanisms in individual patients.The development and clinical implementationof targeted drugs into the management of severeasthma allows for the reduction of the overall cor-ticosteroid load in this patient population. Slisz andVasakova [15] advocate a holistic personalizedapproach to asthma management, which – apartfrom pheno/endotyping – should also include theoverall (systemic) corticosteroid use with proactivedocumentation, prophylaxis and treatment ofcorticosteroid-related adverse events. Timely imple-mentation of the most appropriate targeted treat-ment options based on adequate biomarkers shouldbe part of the approach.In summary, our modern understanding of thepathophysiology, triggers and risk factors of asthmahave allowed us to ‘think differently’ about thisdisease. However, despite great progress in unravel-ling several molecular mechanisms underlying thepathogenesis of asthma and the development ofseveral effective targeted treatment options, severalquestions remain unanswered (Table 1). Ongoingand future clinical studies should address thesequestions with the hope that this will help to furthershape the precision medicine approach to asthma.AcknowledgementsNone.Financial support and sponsorshipNone.Conflicts of interestZ.D. has received honoraria for serving on advisoryboards or as a consultant with ALK, Aquilon, AstraZe-neca, Boehringer-Ingelheim, CSL-Behring, HAL-Allergy,MSD, Sanofi-Genzyme. Her institution has receivedresearch support from Foresee Pharmaceuticals, Novartisand Patara pharma.M.v.d.B. reports research grants paid to his institutionfrom GlaxoSmithKline, Chiesi, Astra Zeneca and TEVAPharma.N.A.H. has received honoraria for serving on advisoryboards or as consultant with GSK, Boehringer Ingelheim(BI), Novartis, Sanofi Genzyme, Regeneron, Astra Zenecaand Genentech. His institution has received researchsupport on his behalf from GSK, BI, Astra Zeneca,Novartis and Sanofi.REFERENCES1. Diamant Z, Vijverberg S, Alving K, et al. Towards clinically applicable biomarkersof asthma – an EAACI position paper. Allergy 2019; 74:1835–1851.2. Sánchez-Garcı́a S, Rial MJ, Domı́nguez-Ortega J. Long and winding road:from infant wheeze to adult asthma. Curr Opin Pulm Med 2020; 26:3–9.3. Bontinck A, Maes T, Joos G. Asthma and air pollution: recent insights inpathogenesis and clinical implications. Curr Opin Pulm Med 2020; 26:10–19.4. Steelant B. Epithelial dysfunction in chronic respiratory diseases, a sharedendotype? Curr Opin Pulm Med 2020; 26:20–26.5. Kozik A, Huang YJ. Ecological interactions in asthma: from environment tomicrobiota and immune responses. Curr Opin Pulm Med 2020; 26:27–32.6. Agusti A, Bel E, Thomas M, et al. Treatable traits: toward precision medicine ofchronic airway diseases. Eur Respir J 2016; 47:410–419.7. Ulrik CS, Vijverberg S, Hanania NA, Diamant Z. Precision medicine andtreatable traits in chronic airway diseases - where do we stand? Curr OpinPulm Med 2020; 26:33–39.8. Pitzner-Fabricius A, Toennesen L, Backer V. Can training induce inflammatorycontrol in asthma, or is it symptom control only? Curr Opin Pulm Med 2020;26:56–61.9. Bahmer T, B€ulow Sand JM, Weckmann M. Lost in transition: biomarkers ofremodeling in patients with asthma. Curr Opin Pulm Med 2020; 26:40–46.10. Rogliani P, Sforza M, Calzetta L. The impact of comorbidities on severeasthma. Curr Opin Pulm Med 2020; 26:47–55.11. van der Veen TA, de Groot LES, Melgert BN. The different faces of themacrophage in asthma. Curr Opin Pulm Med 2020; 26:62–68.12. Gauvreau GM, White L, Davis BE. Anti-alarmin approaches entering clinicaltrials. Curr Opin Pulm Med 2020; 26:69–76.13. Vijverberg SJH, Brinkman P, Rutjes NWP, Maitland-van der Zee AH. Precisionmedicine in severe pediatric asthma: opportunities and challenges. Curr OpinPulm Med 2020; 26:77–83.14. Christenson SA. The role of genomic profiling in identifying molecular phe-notypes in obstructive lung diseases. Curr Opin Pulm Med 2020; 26:84–89.15. Slisz T, Vasakova M. The burden of corticosteroid overload in severe anddifficult to treat asthma: how to reduce this? Curr Opin Pulm Med 2020;26:90–96.Table 1. Unanswered questions to be addressed for novel-targeted asthma therapies (biologics and small molecules)Which pathway should be (preferably) targeted (in the first place)by which biologic or SM in an individual patient with an‘overlapping’ phenotype/endotype?What is the optimal duration for a given therapy in an individualpatient?What are the stopping rules for an individual-targeted therapy?What is the long-term safety of biologics in the general asthmapopulation and selected special populations (e.g. children,pregnant and elderly patients)?What is the feasibility of administering a combination of biologicsand/or SM and will that improve the efficacy and maintainsafety of the therapies?Can chronic use of biologics and/or SM alter the natural course ofthe disease or come close to actually curing the disease?Can the use of biologics and/or SM in high-risk individualsprevent the onset of asthma?SM, small molecules.Asthma2 www.co-pulmonarymedicine.com Volume 26  Number 1  January 2020

NARCIS 

Editorial: Asthma: a modifiable disease on a crossroad

   University of GroningenEditorialDiamant, Zuzana; van den Berge, Maarten; Hanania, Nicola APublished in:Current Opinion in Pulmonary MedicineDOI:10.1097/MCP.0000000000000650IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2020Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Diamant, Z., van den Berge, M., & Hanania, N. A. (2020). Editorial: Asthma: a modifiable disease on acrossroad. Current Opinion in Pulmonary Medicine, 26(1), 1-2.https://doi.org/10.1097/MCP.0000000000000650CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 04-06-2022Downloadedfromhttps://journals.lww.com/co-pulmonarymedicinebyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3mH5nK33R3QitS123Wq8VstcFeB1oKb/CKMiJMDrOyyz0qtOsvBMVXg==on02/14/2020Downloadedfromhttps://journals.lww.com/co-pulmonarymedicinebyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3mH5nK33R3QitS123Wq8VstcFeB1oKb/CKMiJMDrOyyz0qtOsvBMVXg==on02/14/2020 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. CURRENTOPINION Asthma: a modifiable disease on a crossroadZuzana Diamanta,b,c, Maarten van den Berged, and Nicola A. HananiaeWhile asthma is an old disease, we have come a longway to better understanding this syndrome in the lastfew years. More recently, there has been a substantialincrease in our insights into the immunologicalmechanisms underlying the pathogenesis of asthmawhich helped define several phenotypes and endo-types [1]. Along with mapping of several endogenouspathways related to asthma which drive the develop-ment of targeted therapies, an increasing number ofboth external and internal factors inducing or mod-ulating these pathways have also been identified.Our better insight and understanding of ‘modifiable’factors of asthma will likely improve our approach toits management and thus lead to better outcomes inpatients struggling with this disease.In this issue, Sánchez-Garcı́a et al. [2], discuss thepotential risk factors of asthma from in-utero andmaternal exposures to infancy and childhood riskfactors and point out the role of few preventivestrategies that have been studied or need to be exam-ined. Bontinck et al. [3] report on the effects inducedby the exposome, represented by air pollutants, onhuman well being in general and, specifically, onairways and lung health. Air pollutants includingparticulate matter, NO2 and ozone which arise fromroad traffic, industries and other human pollutingactivities, trigger upper and lower airway inflamma-tionand, thus, can bothinduceandexacerbateairwaydiseases such as rhinitis and asthma. In close associa-tion with this topic, Steelant et al. [4] report on theepithelial dysfunction and its consequences onchronic respiratory diseases. Furthermore, interestingnew insights on both external and internal disease-modifying factors, that is the environmental and‘endogenous’ microbiome, are addressed by Kozikand Huang [5]. They discuss several recent findingsunderscoring the accumulating evidence that withindefined time-windows in life, microbiota have animportant (immune) modifying role in asthma path-ogenesis and in shaping the asthma phenotype. Inaddition, they address the interactions of both indoormicrobiome (or aerobiome) and ‘endogenous’ micro-biome with environmental factors (e.g. allergens,ozone, etc) and their effects on asthma.Apart from environmental factors, the clinicalexpression of asthma in individual patients is com-posed of multiple, partly overlapping, pathophysio-logical features and their underlying mechanisms. Toimplement precision medicine into daily practice,Agusti et al. [6] introduced the holistic concept oftreatable traits. The bottom line, this approach comesdown to proactive identification of all disease-relatedcomponents within individual patients that can betreated as part of a personalized management plan. Itthis issue, Ulrik et al. [7] provide an update on thetreatable traits topic, which is being extended to‘treatable mechanisms’ by uncovering underlyingmolecular pathways and identifying reliable bio-markers to further refine targeted treatments in indi-vidual patients. According to Pitzner-Fabricius et al.regular exercise can improve both symptoms andinflammation [8], while both pulmonary and extra-pulmonary comorbidities have a major impacton thecourse of asthma. Bahmer et al. [9] discuss the com-plexity of several aspects of airway remodeling, itschanges throughout the life-cycle and the urgentneed of adequate biomarkers to monitor treatmentrespons in clinical daily practice. Rogliani et al. [10]discuss the importance of accurately identifying andmanaging comorbidities especially in patients withuncontrolled disease.The identification of molecular pathways under-lying type 2 asthma has driven the development ofseveral targeted biologics and small molecules. Alar-mins [IL25, IL33 and thymic stromal lymphopoietin(TSLP)] act upstream in the inflammatory cascadethrough activation of dendritic cells and polarizingT cells to produce type 2 cytokines. In addition, theycan directly activate several effector cells that play aaDepartment of Respiratory Medicine & Allergology, Institute for ClinicalScience, Skane University Hospital, Lund University, Lund, Sweden,bDepartment of Respiratory Medicine, First Faculty of Medicine, CharlesUniversity and Thomayer Hospital, Prague, Czech Republic, cDepartmentof Clinical Pharmacy & Pharmacology, University Groningen, UniversityMedical Center Groningen and QPS-NL, dDepartment of RespiratoryMedicine, University Groningen, University Medical Center Groningen,Groningen, The Netherlands and eSection of Pulmonary and CareMedicine, Airways Clinical Research Center, Baylor College of Medicine,Houston, Texas, USACorrespondence to Prof. Zuzana Diamant, MD, PhD, Department ofClinical Pharmacy & Pharmacology, University Groningen, UniversityMedical Center Groningen and QPS-NL, Hanzeplein 1, Entrance 53,9713 AG Groningen, The Netherlands. Tel: +31 0 50 3048012;e-mail: z.diamant@gems.demon.nlCurr Opin Pulm Med 2020, 26:1–2DOI:10.1097/MCP.00000000000006501070-5287 Copyright  2019 Wolters Kluwer Health, Inc. All rights reserved. www.co-pulmonarymedicine.comEDITORIAL Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.central role in both allergic and nonallergic asthma.As discussed by van der Veen et al. [11], the asth-matic inflammatory process can be shifted towardseither a Th2 or a Th1 environment depending onspecific macrophage subtypes present within theairway wall. Gauvreau et al. [12] discuss the potentialof targeting TSLP in the treatment of type 2 asthma,while blocking IL33 and IL25 may help to definetheir respective role in (the treatment of) asthma. Inline with principles of precision medicine and theincreased emphasis on targeted therapies in patientswith severe asthma, Vijverberg et al. [13] discuss theurgent need of clinically reliable biomarkers to guidetargeted treatment options in pediatric patientswith severe disease. Christenson [14] discusses theuse of specific gene signatures representing path-ways like Th2 and IL17 to explore the presence ofsuch treatable mechanisms in individual patients.The development and clinical implementationof targeted drugs into the management of severeasthma allows for the reduction of the overall cor-ticosteroid load in this patient population. Slisz andVasakova [15] advocate a holistic personalizedapproach to asthma management, which – apartfrom pheno/endotyping – should also include theoverall (systemic) corticosteroid use with proactivedocumentation, prophylaxis and treatment ofcorticosteroid-related adverse events. Timely imple-mentation of the most appropriate targeted treat-ment options based on adequate biomarkers shouldbe part of the approach.In summary, our modern understanding of thepathophysiology, triggers and risk factors of asthmahave allowed us to ‘think differently’ about thisdisease. However, despite great progress in unravel-ling several molecular mechanisms underlying thepathogenesis of asthma and the development ofseveral effective targeted treatment options, severalquestions remain unanswered (Table 1). Ongoingand future clinical studies should address thesequestions with the hope that this will help to furthershape the precision medicine approach to asthma.AcknowledgementsNone.Financial support and sponsorshipNone.Conflicts of interestZ.D. has received honoraria for serving on advisoryboards or as a consultant with ALK, Aquilon, AstraZe-neca, Boehringer-Ingelheim, CSL-Behring, HAL-Allergy,MSD, Sanofi-Genzyme. Her institution has receivedresearch support from Foresee Pharmaceuticals, Novartisand Patara pharma.M.v.d.B. reports research grants paid to his institutionfrom GlaxoSmithKline, Chiesi, Astra Zeneca and TEVAPharma.N.A.H. has received honoraria for serving on advisoryboards or as consultant with GSK, Boehringer Ingelheim(BI), Novartis, Sanofi Genzyme, Regeneron, Astra Zenecaand Genentech. His institution has received researchsupport on his behalf from GSK, BI, Astra Zeneca,Novartis and Sanofi.REFERENCES1. Diamant Z, Vijverberg S, Alving K, et al. Towards clinically applicable biomarkersof asthma – an EAACI position paper. Allergy 2019; 74:1835–1851.2. Sánchez-Garcı́a S, Rial MJ, Domı́nguez-Ortega J. Long and winding road:from infant wheeze to adult asthma. Curr Opin Pulm Med 2020; 26:3–9.3. Bontinck A, Maes T, Joos G. Asthma and air pollution: recent insights inpathogenesis and clinical implications. Curr Opin Pulm Med 2020; 26:10–19.4. Steelant B. Epithelial dysfunction in chronic respiratory diseases, a sharedendotype? Curr Opin Pulm Med 2020; 26:20–26.5. Kozik A, Huang YJ. Ecological interactions in asthma: from environment tomicrobiota and immune responses. Curr Opin Pulm Med 2020; 26:27–32.6. Agusti A, Bel E, Thomas M, et al. Treatable traits: toward precision medicine ofchronic airway diseases. Eur Respir J 2016; 47:410–419.7. Ulrik CS, Vijverberg S, Hanania NA, Diamant Z. Precision medicine andtreatable traits in chronic airway diseases - where do we stand? Curr OpinPulm Med 2020; 26:33–39.8. Pitzner-Fabricius A, Toennesen L, Backer V. Can training induce inflammatorycontrol in asthma, or is it symptom control only? Curr Opin Pulm Med 2020;26:56–61.9. Bahmer T, B€ulow Sand JM, Weckmann M. Lost in transition: biomarkers ofremodeling in patients with asthma. Curr Opin Pulm Med 2020; 26:40–46.10. Rogliani P, Sforza M, Calzetta L. The impact of comorbidities on severeasthma. Curr Opin Pulm Med 2020; 26:47–55.11. van der Veen TA, de Groot LES, Melgert BN. The different faces of themacrophage in asthma. Curr Opin Pulm Med 2020; 26:62–68.12. Gauvreau GM, White L, Davis BE. Anti-alarmin approaches entering clinicaltrials. Curr Opin Pulm Med 2020; 26:69–76.13. Vijverberg SJH, Brinkman P, Rutjes NWP, Maitland-van der Zee AH. Precisionmedicine in severe pediatric asthma: opportunities and challenges. Curr OpinPulm Med 2020; 26:77–83.14. Christenson SA. The role of genomic profiling in identifying molecular phe-notypes in obstructive lung diseases. Curr Opin Pulm Med 2020; 26:84–89.15. Slisz T, Vasakova M. The burden of corticosteroid overload in severe anddifficult to treat asthma: how to reduce this? Curr Opin Pulm Med 2020;26:90–96.Table 1. Unanswered questions to be addressed for novel-targeted asthma therapies (biologics and small molecules)Which pathway should be (preferably) targeted (in the first place)by which biologic or SM in an individual patient with an‘overlapping’ phenotype/endotype?What is the optimal duration for a given therapy in an individualpatient?What are the stopping rules for an individual-targeted therapy?What is the long-term safety of biologics in the general asthmapopulation and selected special populations (e.g. children,pregnant and elderly patients)?What is the feasibility of administering a combination of biologicsand/or SM and will that improve the efficacy and maintainsafety of the therapies?Can chronic use of biologics and/or SM alter the natural course ofthe disease or come close to actually curing the disease?Can the use of biologics and/or SM in high-risk individualsprevent the onset of asthma?SM, small molecules.Asthma2 www.co-pulmonarymedicine.com Volume 26  Number 1  January 2020

   University of GroningenEditorialDiamant, Zuzana; van den Berge, Maarten; Hanania, Nicola APublished in:Current Opinion in Pulmonary MedicineDOI:10.1097/MCP.0000000000000650IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2020Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Diamant, Z., van den Berge, M., & Hanania, N. A. (2020). Editorial: Asthma: a modifiable disease on acrossroad. Current Opinion in Pulmonary Medicine, 26(1), 1-2.https://doi.org/10.1097/MCP.0000000000000650CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 31-10-2023Downloadedfromhttps://journals.lww.com/co-pulmonarymedicinebyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3mH5nK33R3QitS123Wq8VstcFeB1oKb/CKMiJMDrOyyz0qtOsvBMVXg==on02/14/2020Downloadedfromhttps://journals.lww.com/co-pulmonarymedicinebyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3mH5nK33R3QitS123Wq8VstcFeB1oKb/CKMiJMDrOyyz0qtOsvBMVXg==on02/14/2020 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. CURRENTOPINION Asthma: a modifiable disease on a crossroadZuzana Diamanta,b,c, Maarten van den Berged, and Nicola A. HananiaeWhile asthma is an old disease, we have come a longway to better understanding this syndrome in the lastfew years. More recently, there has been a substantialincrease in our insights into the immunologicalmechanisms underlying the pathogenesis of asthmawhich helped define several phenotypes and endo-types [1]. Along with mapping of several endogenouspathways related to asthma which drive the develop-ment of targeted therapies, an increasing number ofboth external and internal factors inducing or mod-ulating these pathways have also been identified.Our better insight and understanding of ‘modifiable’factors of asthma will likely improve our approach toits management and thus lead to better outcomes inpatients struggling with this disease.In this issue, Sánchez-Garcı́a et al. [2], discuss thepotential risk factors of asthma from in-utero andmaternal exposures to infancy and childhood riskfactors and point out the role of few preventivestrategies that have been studied or need to be exam-ined. Bontinck et al. [3] report on the effects inducedby the exposome, represented by air pollutants, onhuman well being in general and, specifically, onairways and lung health. Air pollutants includingparticulate matter, NO2 and ozone which arise fromroad traffic, industries and other human pollutingactivities, trigger upper and lower airway inflamma-tionand, thus, can bothinduceandexacerbateairwaydiseases such as rhinitis and asthma. In close associa-tion with this topic, Steelant et al. [4] report on theepithelial dysfunction and its consequences onchronic respiratory diseases. Furthermore, interestingnew insights on both external and internal disease-modifying factors, that is the environmental and‘endogenous’ microbiome, are addressed by Kozikand Huang [5]. They discuss several recent findingsunderscoring the accumulating evidence that withindefined time-windows in life, microbiota have animportant (immune) modifying role in asthma path-ogenesis and in shaping the asthma phenotype. Inaddition, they address the interactions of both indoormicrobiome (or aerobiome) and ‘endogenous’ micro-biome with environmental factors (e.g. allergens,ozone, etc) and their effects on asthma.Apart from environmental factors, the clinicalexpression of asthma in individual patients is com-posed of multiple, partly overlapping, pathophysio-logical features and their underlying mechanisms. Toimplement precision medicine into daily practice,Agusti et al. [6] introduced the holistic concept oftreatable traits. The bottom line, this approach comesdown to proactive identification of all disease-relatedcomponents within individual patients that can betreated as part of a personalized management plan. Itthis issue, Ulrik et al. [7] provide an update on thetreatable traits topic, which is being extended to‘treatable mechanisms’ by uncovering underlyingmolecular pathways and identifying reliable bio-markers to further refine targeted treatments in indi-vidual patients. According to Pitzner-Fabricius et al.regular exercise can improve both symptoms andinflammation [8], while both pulmonary and extra-pulmonary comorbidities have a major impacton thecourse of asthma. Bahmer et al. [9] discuss the com-plexity of several aspects of airway remodeling, itschanges throughout the life-cycle and the urgentneed of adequate biomarkers to monitor treatmentrespons in clinical daily practice. Rogliani et al. [10]discuss the importance of accurately identifying andmanaging comorbidities especially in patients withuncontrolled disease.The identification of molecular pathways under-lying type 2 asthma has driven the development ofseveral targeted biologics and small molecules. Alar-mins [IL25, IL33 and thymic stromal lymphopoietin(TSLP)] act upstream in the inflammatory cascadethrough activation of dendritic cells and polarizingT cells to produce type 2 cytokines. In addition, theycan directly activate several effector cells that play aaDepartment of Respiratory Medicine & Allergology, Institute for ClinicalScience, Skane University Hospital, Lund University, Lund, Sweden,bDepartment of Respiratory Medicine, First Faculty of Medicine, CharlesUniversity and Thomayer Hospital, Prague, Czech Republic, cDepartmentof Clinical Pharmacy & Pharmacology, University Groningen, UniversityMedical Center Groningen and QPS-NL, dDepartment of RespiratoryMedicine, University Groningen, University Medical Center Groningen,Groningen, The Netherlands and eSection of Pulmonary and CareMedicine, Airways Clinical Research Center, Baylor College of Medicine,Houston, Texas, USACorrespondence to Prof. Zuzana Diamant, MD, PhD, Department ofClinical Pharmacy & Pharmacology, University Groningen, UniversityMedical Center Groningen and QPS-NL, Hanzeplein 1, Entrance 53,9713 AG Groningen, The Netherlands. Tel: +31 0 50 3048012;e-mail: z.diamant@gems.demon.nlCurr Opin Pulm Med 2020, 26:1–2DOI:10.1097/MCP.00000000000006501070-5287 Copyright  2019 Wolters Kluwer Health, Inc. All rights reserved. www.co-pulmonarymedicine.comEDITORIAL Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.central role in both allergic and nonallergic asthma.As discussed by van der Veen et al. [11], the asth-matic inflammatory process can be shifted towardseither a Th2 or a Th1 environment depending onspecific macrophage subtypes present within theairway wall. Gauvreau et al. [12] discuss the potentialof targeting TSLP in the treatment of type 2 asthma,while blocking IL33 and IL25 may help to definetheir respective role in (the treatment of) asthma. Inline with principles of precision medicine and theincreased emphasis on targeted therapies in patientswith severe asthma, Vijverberg et al. [13] discuss theurgent need of clinically reliable biomarkers to guidetargeted treatment options in pediatric patientswith severe disease. Christenson [14] discusses theuse of specific gene signatures representing path-ways like Th2 and IL17 to explore the presence ofsuch treatable mechanisms in individual patients.The development and clinical implementationof targeted drugs into the management of severeasthma allows for the reduction of the overall cor-ticosteroid load in this patient population. Slisz andVasakova [15] advocate a holistic personalizedapproach to asthma management, which – apartfrom pheno/endotyping – should also include theoverall (systemic) corticosteroid use with proactivedocumentation, prophylaxis and treatment ofcorticosteroid-related adverse events. Timely imple-mentation of the most appropriate targeted treat-ment options based on adequate biomarkers shouldbe part of the approach.In summary, our modern understanding of thepathophysiology, triggers and risk factors of asthmahave allowed us to ‘think differently’ about thisdisease. However, despite great progress in unravel-ling several molecular mechanisms underlying thepathogenesis of asthma and the development ofseveral effective targeted treatment options, severalquestions remain unanswered (Table 1). Ongoingand future clinical studies should address thesequestions with the hope that this will help to furthershape the precision medicine approach to asthma.AcknowledgementsNone.Financial support and sponsorshipNone.Conflicts of interestZ.D. has received honoraria for serving on advisoryboards or as a consultant with ALK, Aquilon, AstraZe-neca, Boehringer-Ingelheim, CSL-Behring, HAL-Allergy,MSD, Sanofi-Genzyme. Her institution has receivedresearch support from Foresee Pharmaceuticals, Novartisand Patara pharma.M.v.d.B. reports research grants paid to his institutionfrom GlaxoSmithKline, Chiesi, Astra Zeneca and TEVAPharma.N.A.H. has received honoraria for serving on advisoryboards or as consultant with GSK, Boehringer Ingelheim(BI), Novartis, Sanofi Genzyme, Regeneron, Astra Zenecaand Genentech. His institution has received researchsupport on his behalf from GSK, BI, Astra Zeneca,Novartis and Sanofi.REFERENCES1. Diamant Z, Vijverberg S, Alving K, et al. Towards clinically applicable biomarkersof asthma – an EAACI position paper. Allergy 2019; 74:1835–1851.2. Sánchez-Garcı́a S, Rial MJ, Domı́nguez-Ortega J. Long and winding road:from infant wheeze to adult asthma. Curr Opin Pulm Med 2020; 26:3–9.3. Bontinck A, Maes T, Joos G. Asthma and air pollution: recent insights inpathogenesis and clinical implications. Curr Opin Pulm Med 2020; 26:10–19.4. Steelant B. Epithelial dysfunction in chronic respiratory diseases, a sharedendotype? Curr Opin Pulm Med 2020; 26:20–26.5. Kozik A, Huang YJ. Ecological interactions in asthma: from environment tomicrobiota and immune responses. Curr Opin Pulm Med 2020; 26:27–32.6. Agusti A, Bel E, Thomas M, et al. Treatable traits: toward precision medicine ofchronic airway diseases. Eur Respir J 2016; 47:410–419.7. Ulrik CS, Vijverberg S, Hanania NA, Diamant Z. Precision medicine andtreatable traits in chronic airway diseases - where do we stand? Curr OpinPulm Med 2020; 26:33–39.8. Pitzner-Fabricius A, Toennesen L, Backer V. Can training induce inflammatorycontrol in asthma, or is it symptom control only? Curr Opin Pulm Med 2020;26:56–61.9. Bahmer T, B€ulow Sand JM, Weckmann M. Lost in transition: biomarkers ofremodeling in patients with asthma. Curr Opin Pulm Med 2020; 26:40–46.10. Rogliani P, Sforza M, Calzetta L. The impact of comorbidities on severeasthma. Curr Opin Pulm Med 2020; 26:47–55.11. van der Veen TA, de Groot LES, Melgert BN. The different faces of themacrophage in asthma. Curr Opin Pulm Med 2020; 26:62–68.12. Gauvreau GM, White L, Davis BE. Anti-alarmin approaches entering clinicaltrials. Curr Opin Pulm Med 2020; 26:69–76.13. Vijverberg SJH, Brinkman P, Rutjes NWP, Maitland-van der Zee AH. Precisionmedicine in severe pediatric asthma: opportunities and challenges. Curr OpinPulm Med 2020; 26:77–83.14. Christenson SA. The role of genomic profiling in identifying molecular phe-notypes in obstructive lung diseases. Curr Opin Pulm Med 2020; 26:84–89.15. Slisz T, Vasakova M. The burden of corticosteroid overload in severe anddifficult to treat asthma: how to reduce this? Curr Opin Pulm Med 2020;26:90–96.Table 1. Unanswered questions to be addressed for novel-targeted asthma therapies (biologics and small molecules)Which pathway should be (preferably) targeted (in the first place)by which biologic or SM in an individual patient with an‘overlapping’ phenotype/endotype?What is the optimal duration for a given therapy in an individualpatient?What are the stopping rules for an individual-targeted therapy?What is the long-term safety of biologics in the general asthmapopulation and selected special populations (e.g. children,pregnant and elderly patients)?What is the feasibility of administering a combination of biologicsand/or SM and will that improve the efficacy and maintainsafety of the therapies?Can chronic use of biologics and/or SM alter the natural course ofthe disease or come close to actually curing the disease?Can the use of biologics and/or SM in high-risk individualsprevent the onset of asthma?SM, small molecules.Asthma2 www.co-pulmonarymedicine.com Volume 26  Number 1  January 2020

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Editorial:Asthma: a modifiable disease on a crossroad

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