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World Allergy Forum Symposium:“Precision Medicine”

Program

Moderators: Antonella Muraro (Italy)Lanny Rosenwasser (United States)

Welcome to the World Allergy Forum Symposium and Introduction to “Precision Medicine”Lanny Rosenwasser (United States)

BiobankingGurjit Khurana-Hershey (United States)

Endotypes and PhenotypesEugene Bleecker (United States)

Biodynamics and GenotypesDeborah Meyers (United States)

The World Allergy Organization (WAO) is an international umbrella organization whose members consist of 95 regional and national allergology and clinical immunology societies from around the world.

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Join us forXXIV World Allergy Congress

14–17 October 2015Seoul, Korea

www.worldallergy.org/wac2015

A meeting of in collaboration with and their mutual collaborating partner

Registration Now Open

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“Precision Medicine”Program

Moderators: Antonella Muraro, MDPadua General University HospitalRovigo, Italy

Lanny Rosenwasser, MDChildren’s Mercy Hospital and ClinicsKansas City, MO

1. Welcome to the World Allergy Forum Symposium and Introduction to “Precision Medicine”Lanny Rosenwasser

2. Biobanking Gurjit Khurana-Hershey Children’s Hospital Medical Center Cincinnati, OH

3. Endotypes and Phenotypes Eugene Bleecker Wake Forest University School of Medicine

Winston-Salem, NC

4. Biodynamics and Genotypes Deborah Meyers Wake Forest University School of Medicine

Winston-Salem, NC

2014-2015 World Allergy Form Advisory Board

ChairLanny Rosenwasser, United States

Vice ChairMario Sanchez-Borges, Venezuela

MembersCezmi Akdis, SwitzerlandA. Wesley Burks, United StatesFrancesca Levi Schaffer, IsraelJames Li, United StatesDean Metcalfe, United StatesNikos Papadopoulos, GreeceRuby Pawankar, JapanSusan Prescott, AustraliaNelson Rosario, Brazil

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About WAOThe World Allergy Organization (WAO) is an international alliance of 95 global, regional and national allergy, asthma and clinical immunology societies. Through collaboration with the Member Societies, WAO provides a wide range of educational and outreach programs, symposia and lectureships to allergists/immunologists around the globe and conducts initiatives relating to clinical practice, service provision, and physician training in order to better understand and address the challenges facing allergists/immunologists worldwide.

Mission Of The World Allergy OrganizationWAO’s mission is to be a global resource and advocate in the field of allergy and asthma, advancing excellence in clinical care through education, research and training as a world-wide alliance of allergy, asthma and clinical immunology societies.

WAO MeetingsWorld Allergy Congress™ (WAC)WAO hosts the World Allergy Congress ™ (WAC) – its main scientific meeting – biennially in different regions of the world. Please join us in Seoul, South Korea from 14-17 October 2015.

WAO International Scientific Conference (WISC)WAO International Scientific Conference (WISC) is a theme-based Scientific Conference alternating with and complementing WAO’s biennial scientific meeting, the World Allergy Congress (WAC). Please join us in Jerusalem, Israel from in December 2016.

SymposiaThe WAO Symposium is a focused, two-day meeting which summarizes what is scientifically known, explores cutting-edge research, and recognizes unmet needs. Simultaneous tracks are offered to attendees. Each track offers compelling lectures, presentations and discussions presented by top international leaders and experts in the field. A WAO Symposium will be held in Miami, FL, USA during 5-6 December 2015 with a focus on Food Allergy and the Microbiome.

World Allergy Organization JournalThe World Allergy Organization Journal (WAO Journal) provides a global forum for the exchange of research and information on allergy, asthma, and clinical immunology. The journal supports this scientific interaction among members of the World Allergy Organization, an alliance of 95 societies worldwide, through publication of original research, clinical reviews, position papers, and epidemiological studies that contribute to current knowledge in patient care. Articles cover diagnosis, therapeutic options, crisis management, and treatment efficacy. Authors and reviewers represent all geographic regions, providing a truly global perspective. www.waojournal.org

WAO Online ResourcesAs a leading global online destination for allergy, asthma and clinical immunology the WAO website supports and enhances WAO educational activities and provides materials specifically designed for continued learning and reference.

Popular resources include: • Specially commissioned educational synopses on major topics posted in the Allergic Diseases Resource Center• Interactive case studies that challenge allergists to diagnose unusual cases• Online learning programs including the Immunology Online Lecture Series, Asthma and Allergic Rhinitis Online Lecture Series, Co-morbidities of Asthma and AR

Online Lecture Series, and the case-based interactive learning modules on Allergic Rhinitis with Asthma, Management of Asthma with Co-Morbid AR, Chronic Urticaria/Angioedema, Idiopathic Anaphylaxis, Insect Venom Hypersensitivity, Latex Allergy, Severe Asthma, Drug Allergy, Food Allergy, and Allergic Rhinitis

• An archive of webinars recorded at major meetings, and audio recordings of interviews with key opinion leaders around the world• Defining the Specialty, a section that provides easy access to WAO publications and other resources that help to define the specialty of allergy and

immunology including the WAO White Book on Allergy: Update 2013• Disease-specific sections of the website including the Allergic Rhinitis Working Group, Anaphylaxis, Small Airways Working Group, HAE International Alliance,

and Eosinophils, Mast Cells, and Basophils in Allergic Diseases• World Atlas of Aeroallergens

The WAO website is HONcode certified. www.worldallergy.org

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World Allergy Organization • 555 E. Wells St., Suite 1100 • Milwaukee, WI 53202-3823 • USAPhone: +1 414 276 1791 • Fax: +1 414 276 3349 • E-mail: info@worldallergy.org • www.worldallergy.org

WAO Programs For Education, Research And Patient CareWorld Allergy Forum ® (WAF)The World Allergy Forum ® (WAF) program brings cutting edge symposia to major allergy meetings throughout the world. Developed by international expert advisory panels, the symposia provide up-to-the minute presentations on scientific and clinical developments in the field of allergic disease. WAF is the longest running educational program series sponsored by WAO and currently provides two or three placements a year with up to 1,000 attendees at each program. WAF is supported by an unrestricted educational grant from Novartis. View presentations for free at www.worldallergy.org/waf.

Emerging Societies Program (ESP) In order to advance the WAO mission of supporting developments that will enable allergists to better serve patients now and in the future, the Emerging Societies Program (ESP) aims to disseminate information on and share experiences about new treatments for allergic disease and about new indications for available therapies. As a response to an area of need identified by ESP Delegates, the ESP has also started to offer World Allergy Training Schools (WATS) in various regions of the world. All ESP meetings and training schools are conducted with the help and support of WAO Member Societies and held in conjunction with a Member Society’s annual meeting and in partnership with the American College of Allergy, Asthma and Immunology (ACAAI). View all ESP activities at www.worldallergy.org/.

WAO PublicationsWAO papers support and promote the specialty of allergy and help set standards for clinical practice and training. A full bibliography is available at www.worldallergy.org/publications/.

World Allergy WeekWorld Allergy Week is an annual initiative of the World Allergy Organization (WAO), together with its Member Societies, to raise awareness of allergic disease and related disorders and advocate for the provision of training and resources in the diagnosis, management, and prevention of these diseases and asthma, which are rising in prevalence worldwide.

WAO established the initiative with the vision of bringing together multiple stakeholder groups including physicians, medical educators, patient advocates, policy makers, the general public, and health care authorities for an integrated approach to addressing the needs of patients who suffer from allergic diseases and asthma and those who provide care for them.

There are many ways to get involved. Each year WAO receives stories, audio and video recordings, photographs and press releases from the many programs and activities that take place locally, nationally and regionally due to the innovative planning of participating individuals and organizations. Many of these reports are archived on this website.

WAO provides resources every year regarding the global theme for its Member Societies and information for everyone interested in World Allergy Week. Learn more at www.worldallergyweek.org.

World Allergy Week 2015 will be from 13-19 April 2015 and will bring awareness to Airway Allergies – The Human and Economic Burden.

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WAo MeMber SocietieS

Albanian Society of Allergology and Clinical ImmunologyNational Association for Private Algerian AllergistsAmerican Academy of Allergy, Asthma and Immunology American College of Allergy, Asthma and Immunology Argentine Association of Allergy and Immunology Argentine Society of Allergy and Immunopathology Australasian Society of Clinical Immunology and Allergy Austrian Society of Allergology and Immunology Azerbaijan Society for Asthma, Allergy and Clinical Immunology Bangladesh Society of Allergy and Immunology Belarus Association of Allergology & Clinical ImmunologyBelgian Society for Allergy and Clinical Immunology Brazilian Society of Allergy and Immunopathology British Society for Allergy and Clinical Immunology Bulgarian Society of Allergology Canadian Society of Allergy and Clinical Immunology Chilean Society of Allergy and Immunology Chinese Society of Allergy and Immunology Colombian Allergy, Asthma, and Immunology Association Croatian Society of Allergology and Clinical Immunology Cuban Society of Allergology Czech Society of Allergology and Clinical Immunology Danish Society of Allergology Dutch Society of AllergologyEgyptian Society of Allergy and Clinical Immunology Egyptian Society of Pediatric Allergy and ImmunologyFinnish Society of Allergology and Clinical Immunology French Society of Allergology Georgian Association of Allergology and Clinical Immunology German Society for Allergology and Clinical Immunology Hellenic Society of Allergology and Clinical Immunology Honduran Society of Allergy and Clinical ImmunologyHong Kong Institute of AllergyHungarian Society of Allergology and Clinical Immunology Icelandic Society of Allergy and Immunology Indian College of Allergy, Asthma and Applied Immunology (ICAAI) Indonesian Society for Allergy and Immunology Iranian Society of Asthma and Allergy Israel Association of Allergy and Clinical Immunology

Italian Association of Territorial and Hospital AllergistsItalian Society of Allergy and Clinical Immunology Japanese Society of Allergology Jordanian Society for Allergy and Clinical ImmunologyKorean Academy of Allergy, Asthma and Clinical Immunology Kuwait Society of Allergy and Clinical ImmunologyLatvian Association of AllergistsLebanese Society of Allergy and Immunology Malaysian Society of Allergy and Immunology Mexican College of Clinical Immunology and AllergyMexican College of Pediatricians in Allergy and Clinical ImmunologyMoldavian Society of Allergology and ImmunologyMongolian Society of AllergologyMoroccan Society of Allergology and Clinical Immunology Netherlands Society of Allergology Panamanian Association of Allergology and Clinical ImmunologyParaguayan Society of Immunology and AllergyPeruvian Society of Allergy and Immunology Philippine Society of Allergy, Asthma and Immunology Polish Society of Allergology Portuguese Society of Allergology and Clinical Immunology Romanian Society of Allergology and Clinical Immunology Russian Association of Allergology and Clinical Immunology Serbian Association of Allergologists and Clinical ImmunologistsAllergy and Clinical Immunology Society (Singapore) Slovenian Association for Allergology and Clinical ImmunologyAllergy Society of South Africa Spanish Society of Allergology and Clinical Immunology Allergy and Immunology Society of Sri LankaSwedish Association for AllergologySwiss Society for Allergology and Immunology Allergy, Asthma and Immunology Society of Thailand Tunisian Society of Respiratory Diseases and AllergologyTurkish National Society of Allergy and Clinical Immunology Ukrainian Association of Allergologists and Clinical ImmunologistsUruguayan Society of Allergology Venezuelan Society of Allergy, Asthma and Immunology Vietnam Association of Allergy, Asthma and Clinical Immunology Zimbabwe Allergy Society

The World Allergy Organization (WAO), a world federation of allergy, asthma, and clinical immunology societies, consists of 95 Member Societies. All active members of dues-paying Member Societies are Individual Members of WAO.

Apply for your National Allergy Society to become a WAO Member Society at www.worldallergy.org/wao_societies/apply.php.

British Society for ImmunologyGlobal Allergy and Asthma European NetworkInternational Association of Asthmology

International Primary Care Respiratory GroupSouthern European Allergy Societies

Allergy Society of KenyaArmenian Association of Immunology and AllergyEcuadorian Society of Allergy, Asthma, and Immunology Guatemalan Allergy, Asthma and Clinical Immunology Association

Indian Academy of AllergyTaiwan Academy of Pediatric Allergy Asthma ImmunologyUkrainian Allergists Association

ASSociAte MeMber SocietieS

regionAl orgAnizAtionSAsia Pacific Association of Allergy, Asthma and Clinical ImmunologyAsia Pacific Association of Pediatric Allergy, Respirology and ImmunologyCommonwealth of Independent States Society of Immunology and Allergology

European Academy of Allergology and Clinical ImmunologyLatin American Society of Allergy and Immunology

AffiliAte orgAnizAtionS

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8 June 2015

Dear Colleagues,

A warm welcome to the forty-eighth symposium in the World Allergy Forum (WAF) Series: Precision Medicine. Recognizing the importance of severe airway diseases, the World Allergy Organization (WAO) is delighted to bring this symposium to the 2015 Annual EAACI Congress in Barcelona, Spain.

WAO is proud to announce that the year 2015 marks the 18th anniversary of the World Allergy Forum. WAO is appreciative that this symposium is an annual event at the EAACI Annual Congress. Since 1997, WAF has flourished and become the longest continuing educational program of World Allergy Organization (WAO).

With the increasing prevalence of severe asthma globally, there is an urgent need to understand the severity of airway function disruption in asthma. This World Allergy Forum will focus on the novel concepts of immune and airway function with this symposium entitled, “Precision Medicine.”

We have three outstanding physicians speaking in today’s symposium. The first, Dr. Gurjit Khurana-Hershey, will talk about collection of patient-oriented data and Biobanking. The second will be offered by Dr. Eugene Bleecker, who will look at “Endotypes and Phenotypes”. The third presentation will be given by Dr. Deborah Meyers who will examine treatment strategies in the talk entitled, “Biodynamics and Genotypes.” There will be an informal discussion to follow the lectures.

The WAO Board hopes that you enjoy today’s outstanding symposium maintaining the high standards the World Allergy Forum has set since 1997. To view past WAF presentations and today’s symposium please go to the following webpage: http://www.worldallergy.org/educational_programs/world_allergy_forum/

On behalf of the Board of Directors, WAO would like to thank the EAACI for this opportunity to host this WAF session at their Annual Congress. WAO also gratefully acknowledges the unrestricted educational grant from Novartis that supports educations programs such as this conjoint program at the EAACI congress.

With best regards,

Lanny Rosenwasser, MD Antonella Muraro, MDPresident President-ElectWorld Allergy Organization European Academy of Allergy and Clinical Immunology

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Biobanking

Dr. Gurjit Khurana-HersheyChildren’s Hospital Medical CenterCincinnati, OH

BACKGROUND AND OBJECTIVE: Asthma heterogeneity causes difficulty in studying and treating the disease. We built a abstract comprehensive statewide repository linking questionnaire and medical record data with health outcomes to characterize the variability of clinical practices at Ohio children’s hospitals for the treatment of hospitalized asthma.

METHODS: Children hospitalized at 6 participating Ohio children’s hospitals for asthma exacerbation or reactive airway disease aged 2 to 17 were eligible. Medical, social, and environmental histories and past asthma admissions were collected from questionnaires and the medical record.

RESULTS: From December 2012 to September 2013, 1012 children were enrolled. There were significant differences in the population served, emergency department and inpatient practices, intensive care unit usage, discharge criteria, and length of stay across the sites (all P , .0001, total n = 1012). Public insurance was highest in Cleveland and Cincinnati (72 and 65%). In the emergency department, Cincinnati and Akron had the highest intravenous magnesium sulfate use (37% and 33%); Columbus administered the most intramuscular epinephrine (15%). Cleveland and Columbus had the highest intensive care unit admittance (44% and 41%) and proportion of long-stay patients (95% and 85%). Moderate/severe asthma severity classification was associated with discharge prescription for inhaled corticosteroids (odds ratio = 2.7; 95% confidence interval: 1.6–4.5; P = .004) but not stay length.

CONCLUSIONS: These data highlight the need for standardization of treatment practices for inpatient asthma care. There is considerable opportunity for personalized care plans that incorporate a patient’s asthma impairment, risk, and treatment response history into hospital practices for asthma exacerbation treatment. The Ohio Pediatric Asthma Repository is a unique statewide resource in which to conduct observational, comparative effectiveness, and ultimately intervention studies for pediatric asthma.

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References:1. Centers for Disease Control and Prevention. Vital signs. Asthma in the US: growing every year. May 2011. Available at: http://www.cdc.gov/VitalSigns/Asthma/. Accessed November 25, 2014

2. Akinbami L; Centers for Disease Control and Prevention National Center for Health Statistics. The state of childhood asthma, United States, 1980–2005. Adv Data. 2006;(381):1–24

3. American Lung Association. Asthma & Children Fact Sheet. Chicago, IL: American Lung Association; October 2012

4. Ohio Department of Health Asthma Program; Ohio Surveillance System for Asthma. Burden of Asthma in Ohio, 2012. Columbus, OH: Ohio Department of Health Asthma Program; 2012

5. Sly RM. Changing prevalence of allergic rhinitis and asthma. Ann Allergy Asthma Immunol. 1999;82(3):233–248, quiz 248–252

6. Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ; The Group Health Medical Associates. Asthma and wheezing in the first six years of life. N Engl J Med. 1995;332(3):133–138

7. Drazen JM, Silverman EK, Lee TH. Heterogeneity of therapeutic responses in asthma. Br Med Bull. 2000;56(4):1054–1070

8. Fassl BA, Nkoy FL, Stone BL, et al. The Joint Commission Children’s Asthma Care quality measures and asthma readmissions. Pediatrics. 2012;130(3):482–491

9. Reddel H, Ware S, Marks G, Salome C, Jenkins C, Woolcock A. Differences between asthma exacerbations and poor asthma control. Lancet. 1999;353(9150):364–369

10. Butsch Kovacic M, Biagini Myers JM, Lindsey M, et al. The Greater Cincinnati Pediatric Clinic Repository: A Novel Framework for Childhood Asthma and Allergy Research. Pediatr Allergy Immunol Pulmonol. 2012;25(2):104–113

11. Biagini Myers JM, Khurana Hershey GK, Deka R, et al. Asking the right questions to ascertain early childhood secondhand smoke exposures. J Pediatr. 2012;160(6): 1050–1051

12. National Asthma Education and Prevention Program; National Heart, Lung, and Blood Institute. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. NIH Publication No. 07-4051. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute; 2007

13. Cohen ME, Dimick JB, Bilimoria KY, Ko CY, Richards K, Hall BL. Risk adjustment in the American College of Surgeons National Surgical Quality Improvement Program: a comparison of logistic versus hierarchical modeling. J Am Coll Surg. 2009;209(6):687–693

14. Bishaw A. Areas with concentrated poverty: 2006–2010. US Department of Commerce. Economics and Statistics Administration. 2011. Available at: www.census.gov/prod/2011pubs/acsbr10-17.pdf. Accessed November 25, 2014

15. Kinsman L, Rotter T, James E, Snow P, Willis J. What is a clinical pathway? Development of a definition to inform the debate. BMC Med. 2010;8:31

16. Sylvester AM, George M. Effect of a Clinical Pathway on Length of Stay and Cost of Pediatric Inpatient Asthma Admissions: An Integrative Review. Clin Nurs Res. 2013;23(4):384–401

17. Banasiak NC, Meadows-Oliver M. Inpatient asthma clinical pathways for the pediatric patient: an integrative review of the literature. Pediatr Nurs. 2004;30(6):447–450

18. McCarthy D, Cohen A, Bihrle Johnson M. Gaining Ground: Care Management Programs to Reduce Hospital Admissions and Readmissions Among Chronically Ill and Vulnerable Patients. New York, NY: The Commonwealth Fund; January 2013

19. Bhogal S, Bourbeau J, McGillivray D, Benedetti A, Bartlett S, Ducharme F. Adherence to pediatric asthma guidelines in the emergency department: a survey of knowledge, attitudes and behaviour among health care professionals. Can Respir J. 2010;17(4):175–182

20. Public Law No. 111-148: H.R. 3590. The Patient Protection and Affordable Care Act. March 23, 2010

21. Manchikanti L, Caraway DL, Parr AT, Fellows B, Hirsch JA. Patient Protection and Affordable Care Act of 2010: reforming the health care reform for the new decade. Pain Physician. 2011;14(1):E35–E67

22. Krishnan JA, Schatz M, Apter AJ. A call for action: Comparative effectiveness research in asthma. J Allergy Clin Immunol. 2011;127(1):123–127

23. Hernán MA, Robins JM. Estimating causal effects from epidemiological data. J Epidemiol Community Health. 2006; 60(7):578–586

24. Howrylak JA, Spanier AJ, Huang B, et al. Cotinine in children admitted for asthma and readmission. Pediatrics. 2014;133(2). Available at: www.pediatrics.org/cgi/content/full/133/2/e355

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Endotypes and Phenotypes

Dr. Eugene BleeckerWake Forest University School of Med.Winston-Salem, NC

Many common diseases are heterogeneous and identification of subpopula-tions is necessary to develop personalized therapeutic strategies. Asthma is an excellent example of a heterogeneous disease with different severity pheno-types and endotypes. It is important to understand that these approaches are applicable to many common diseases. This discussion will include examples of how to subphenotype a disease and identify subpopulations that are based on individual characteristics. Two examples will be used: cluster analysis of clinical data from well phenotyped subjects with mild to severe asthma and a similar analysis of sputum data in the same subjects. These approaches will be contrasted with more traditional classifications of asthma into mild, moderate, and severe persistent disease categories that are used in current treatment guidelines. The results of unbiased cluster classification in asthma will be informative to understand disease endotypes such as eosinophil or TH2 asthma subpopulations. Discretion of asthma into appropriately characterized subphenotypes and endotypes represent the basis for future therapeutic preci-sion strategies.

ReferencesPrescott G. Woodruff, Homer A. Boushey, Gregory M. Dolganov, Chris S. Barker, Yee Hwa Yang, Samantha Donnelly, Almut Ellwanger, Sukhvinder S. Sidhu, Trang P. Dao-Pick, Carlos Pantoja, David J. Erle, Keith R. Yamamoto, and John V. Fahy. Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids. Proc Natl Acad Sci U S A 2007; 104(40):15858-63.

Haldar P, Pavord ID. Noneosinnophilic asthma: a distinct clinical and pathologic phenotype. J Allergy Clin Immunol 2007;119-1043-1052. (quiz 1053-1054).

Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H, Li X, D’Agostino R Jr, Castro M, Curran-Everett D, Fitzpatrick AM, Gaston B, Jarjour NN, Sorkness R, Calhoun WJ, Chung KF, Comhair SAA, Dweik RA, Israel E, Peters SP, Busse WW, Erzurum SC, Bleecker ER for the National Heart Lung Blood Institute’s Severe Asthma Research Program. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Resp Crit Care Med 2010;181:315-323.

Hastie AT, Moore WC, Li H, Rector BM, Pascual RM, Peters SP, Meyers DA, Bleecker ER, NHLBI Severe Asthma Research Program (SARP). Biomarker surrogates do not accurately predict sputum eosinophils and neutrophils in asthma. J Allergy Clin Immunol 2013; 132:72-80.e12.

Moore WC, Hastie AT, Li X, Li H, Busse WW, Jarjour NN, Wenzel SE, Peters SP, Meyers DA, Bleecker ER for the National Heart Lung Blood Institute’s Severe Asthma Research Program. Sputum neutrophils are associated with more severe asthma phenotypes using cluster analysis. J Allergy & Clin Immunol. 2014 133:1557:1563

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Dr. Deborah MeyersWake Forest University School of Med.Winston-Salem, NC

Biodynamics and Genotypes

This talk will focus on the principles of precision medicine or personalized medicine using genetic data. Genetic studies in asthma will be used as an example but these approaches are applicable to any common disease where genetics is important. Two approaches are needed: genetic susceptibility to disease and genetic susceptibility to developing more severe disease. Literature in both areas will be briefly reviewed with examples of multigene models. An additional area of focus will be pharmacogenetics where an individual’s genetic profile is used to predict response to a given therapy in terms of both favorable responses and adverse effects.

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