Asthma Airways and the Environment Putting it all together2shoesapp.com/event_files/31050102054311....

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Asthma Airways and the Environment Putting it all together

Joan Reibman, MD Professor of Medicine and Environmental Medicine Medical Director, WTC Environmental Health Center Medical Director, NYU Asthma Airways Environment Program New York University School of Medicine and Bellevue Hospital

Disclosures

Novartis Genentech AstraZeneca Teva Pharmaceuticals American Lung Association Asthma/Airways Clinical Research Center NIH - NIEHS CDC – NIOSH

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• NYU/Bellevue Hospital Asthma Program • Goal to reduce morbidity and promote understanding of

asthma in the urban population • Access to care/Cost/Environment/Genetic/Socioeconomic

NYC had highest morbidity and mortality for asthma in the US in 1990s

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Asthma hospitalizations and deaths in US

• Asthma Hospitalization relatively stable since 2004

Asthma Hospitalizations Asthma Deaths

• Asthma hospitalization rates decreased nationally • Asthma hospitalization rates decreased by 17% among NYC

residents between 1990 and 2000

CDC National Hospital Discharge Survey and National Vital Statistics

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Individuals with uncontrolled asthma in the US

CDC Asthma Data updated March 2016, (National Health Interview Survey 2014)

• 50% of adults had uncontrolled asthma • 38% of children had uncontrolled asthma • Access to care/Cost/Environment/Genetic/Socioeconomic

The interaction between our environment and mechanisms of asthma and COPD

Understanding these interactions will promote improved management of airways diseases

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Mechanisms of asthma and COPD

Lambrecht and Hammad Nat Immunol 16: 2015

• Multiple pathways of airway inflammation/remodeling

• Redundant

pathways

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Type 2 immune response


• Innate-adaptive immune pathways

• Th2 cell

Th2

Monica Kraft

Dendritic cell

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• Th2 cells • B cell isotype

switching

• IgE

• Eosinophil recruitment/activation

Th2 IgE

Eosinophil

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• Innate Lymphoid Cells

• Eosinophil

recruitment/activation

Innate lymphoid

Cell

Eosinophil

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Type 2 and Non-Type 2 immune responses

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Phenotypic heterogeneity of asthma

Group 1: normal lung function, early onset, few with exacerbations, atopic Group 2: normal lung function, early onset Group 3: late onset, older, less atopic, obese Group 4: low lung function, later onset, highest IgE, atopy, peripheral eos Group 5: lowest lung function, later onset, most on multiple controllers

Severe Asthma Research Program (n = 726)

NYU/Bellevue Registry (n = 471)

Patrawalla, Kazeros, Rogers, Shao, Liu, Shang Fernandez-Beros, Reibman PlosONE 7: 2012

Moore et al. Am J Respir Crit Care Med. 2010

Phenotypic heterogeneity of COPD

Byron Thomashow • GOLD Classification

· FEV1

· Exacerbations · Functional status

• Symptoms • Emphysema • Biologic pathways ?eosinophils

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Drug targets for Type 2 immune diseases


IgE

Anti-IgE Approved Phenotype Allergic asthma

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Anti IL-5 Approved Under development Phenotype Eosinophilic asthma Eosinophilic COPD?

IL-5 IL-5 Eosinophils

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Anti-IL-13 Under development Phenotype Type 2 asthma? COPD?

IL-13 IL-13

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Anti-IL4Ra Under development Phenotype Type 2 asthma? Atopic dermatitis

IL-13 IL-13

IL-13 IL-4

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Innate lymphoid

Cell

CRTH2 Under development Phenotype Type 2 asthma

CRTH2

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Epithelial cell targets Anti-TSLP Under development Phenotype Type 2 asthma

IL-33 TSLP

IL-33 TSLP

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Drug Targets for Non-Type 2 immune responses?

New approaches for airway diseases

Samaan Rafeq • Airway interventions for asthma

· Large airways

· Bronchial thermoplasty

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New approaches for airway diseases

Ken Berger • Small airways

· Detection of small airway function · Detection of environmental lung injury

· Treatment target?

22 Weibel, Morphometry of the Human Lung, Springer 1963

Altered microbiome and immune responses in asthma/COPD

Martin Blaser

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Segal, Clemente, Wu, Wikoff, Gao, Ko, Li, Rom, Blaser Thorax, 2017

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Interaction between allergic disease and pollutants


Gurjit Khurana-Hershey

Pollutants

IL-33 TSLP

IL-33 TSLP

Allergens

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Environmental pollutants and airway diseases


Michael Weitzman

Tobacco

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Mary Rice

Tobacco Trafficc

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Iyad Khierbek

Tobacco Fuel combustion

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Joseph Allen

Tobacco Indoor pollutants

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Public health/environment measures to reduce airway diseases


Indoor Fuel Traffic Tobacco

If you’re not part of the solution You’re part of the precipitate

Thank you

Educational grant from Astra Zeneca Trainee grant from Five Partners Foundation American Lung Association All our exhibitors

Thank you Gail Schattner Marla Hymes Ewa Rakowski Shilpi Ahuja Kathleen Doo Sheila Smyth-Giambanco Dan Sterman CME office

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