Understanding the pathophysiology of severe asthma to generate new therapeutic opportunities Stephen T. Holgate, MD, FMedSci, John Holloway, PhD, Susan.

Slides:

Advertisements

Similar presentations

Early exposure to cow's milk protein is protective against IgE-mediated cow's milk protein allergy Yitzhak Katz, MD, Nelly Rajuan, MSc, Michael R. Goldberg,

Advertisements

Control of immunopathology during chikungunya virus infection Caroline Petitdemange, PhD, Nadia Wauquier, PhD, Vincent Vieillard, PhD Journal of Allergy.

Peter Vadas, MD, PhD, Boris Perelman, PhD, Gary Liss, MD, MS

What drives prescription patterns in pediatric asthma management?

What effect does asthma treatment have on airway remodeling

Asthma exacerbations: Origin, effect, and prevention

Seema S. Aceves, MD, PhD Journal of Allergy and Clinical Immunology

Obstructive sleep apnea syndrome and inflammation

Epigenetic mechanisms silence a disintegrin and metalloprotease 33 expression in bronchial epithelial cells Youwen Yang, PhD, Hans Michael Haitchi, MD,

Santa Jeremy Ono, BA, PhD, Mark B. Abelson, MD

Disparities in allergic disease: Hypersensitivity and social disorders

Dorothy M. Ryan, MD, Stephen J. Fowler, MD, Robert M. Niven, MD

Is 9 more than 2 also in allergic airway inflammation?

Advances in basic and clinical immunology in 2011

Stanley J. Szefler, MD, Richard J. Martin, MD

Mothers' anxiety during pregnancy is associated with asthma in their children Hannah Cookson, MB, ChB, Raquel Granell, PhD, Carol Joinson, PhD, Yoav Ben-Shlomo,

Airway smooth muscle remodeling is a dynamic process in severe long-standing asthma Muhannad Hassan, MD, Taisuke Jo, MD, PhD, Paul-André Risse, PhD,

Lieuwe D. Bos, MSc, PhD, Peter J. Sterk, MD, PhD, Stephen J

Allergy testing in predicting outcome of open food challenge to peanut

The Wiskott-Aldrich syndrome

Peter M. Wolfgram, MD, David B. Allen, MD

An age-dependent association of mannose-binding lectin-2 genetic variants on HIV-1– related disease in children Kumud K. Singh, PhD, Alexis Lieser, MD,

René van Gent, MD, Cornelis K. van der Ent, MD, PhD, Maroeska M

Induction of a disintegrin and metalloprotease 33 during embryonic lung development and the influence of IL-13 or maternal allergy Hans Michael Haitchi,

Phillip Lieberman, MD, Michael Tankersley, MD

Airway smooth muscle remodeling is a dynamic process in severe long-standing asthma Muhannad Hassan, MD, Taisuke Jo, MD, PhD, Paul-André Risse, PhD,

Time for a paradigm shift in asthma treatment: From relieving bronchospasm to controlling systemic inflammation Leif Bjermer, MD Journal of Allergy.

Food allergy in patients with primary immunodeficiency diseases: Prevalence within the US Immunodeficiency Network (USIDNET) Karen S. Tuano, MD, Jordan.

What are the best outcome measurements for atopic eczema

Inhaled allergen bronchoprovocation tests

Augmented epithelial endothelin-1 expression in refractory asthma

The role of the mast cell in the pathophysiology of asthma

Food allergy: A review and update on epidemiology, pathogenesis, diagnosis, prevention, and management Scott H. Sicherer, MD, Hugh A. Sampson, MD Journal.

Biosimilars and drug development in allergic and immunologic diseases

Breakdown in epithelial barrier function in patients with asthma: Identification of novel therapeutic approaches Emily J. Swindle, PhD, Jane E. Collins,

Peter Vadas, MD, PhD, Boris Perelman, PhD, Gary Liss, MD, MS

Claus Bachert, MD, PhD, Cezmi A. Akdis, MD

CC chemokine receptors CCR1 and CCR4 are expressed on airway mast cells in allergic asthma Kawa Amin, PhD, Christer Janson, MD, PhD, Ilkka Harvima, MD,

Effect of ingested H1 antihistamines on methacholine challenge

What is an “eosinophilic phenotype” of asthma?

Weiguo Chen, PhD, Gurjit K. Khurana Hershey, MD, PhD

What the asthma end points we know and love do and do not tell us

H. William Kelly, PharmD Journal of Allergy and Clinical Immunology

Autophagy: Nobel Prize 2016 and allergy and asthma research

Expression of smooth muscle and extracellular matrix proteins in relation to airway function in asthma Annelies M. Slats, MD, Kirsten Janssen, BHe, Annemarie.

Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment

Advances in the approach to the patient with food allergy

Geographic variability in childhood asthma prevalence in Chicago

Airway remodeling in asthma: New insights

Benjamin Chaigne, MD, Hervé Watier, MD, PhD

The National Institutes of Allergy and Infectious Diseases networks on asthma in inner- city children: An approach to improved care William W. Busse,

Martin Brasholt, MD, Florent Baty, PhD, Hans Bisgaard, MD, DMSci

Eosinophilic esophagitis treated with immunotherapy to dust mites

Pathophysiology of asthma: What has our current understanding taught us about new therapeutic approaches? Stephen T. Holgate, MD, FMedSci Journal of.

Advances in basic and clinical immunology in 2013

Emily M. DeBoer, MD, David R. Spielberg, MD, MHSc, Alan S. Brody, MD

Managing asthma exacerbations in the emergency department: Summary of the National Asthma Education and Prevention Program Expert Panel Report 3 guidelines.

Macrolide antibiotics and asthma treatment

Cure of HIV infection: Is the long wait over?

Immune pathomechanism of drug hypersensitivity reactions

Statistical issues in clinical trials that involve the double-blind, placebo-controlled food challenge Vernon M. Chinchilli, PhD, Laura Fisher, MD, Timothy.

Asthma: The past, future, environment, and costs

Asthma Control Test: Reliability, validity, and responsiveness in patients not previously followed by asthma specialists Michael Schatz, MD, MS, Christine.

Environmental factors and eosinophilic esophagitis

Lisa A. Beck, MD, Sarbjit Saini, MD

Advances in pediatric asthma in 2007

News Beyond Our Pages Journal of Allergy and Clinical Immunology

Natural history of cow’s milk allergy

Primary prevention of asthma and allergy

Advances in basic and clinical immunology in 2016

Presentation transcript:

Understanding the pathophysiology of severe asthma to generate new therapeutic opportunities Stephen T. Holgate, MD, FMedSci, John Holloway, PhD, Susan Wilson, PhD, Peter H. Howarth, MD, FRCP, Hans Michael Haitchi, MD, Suresh Babu, MD, Donna E. Davies, PhD Journal of Allergy and Clinical Immunology Volume 117, Issue 3, Pages 496-506 (March 2006) DOI: 10.1016/j.jaci.2006.01.039 Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 1 Effect of entanercept administered for 12 weeks on symptoms (A) and methacholine hyperresponsiveness measured as PC20 (B) in patients with severe corticosteroid-refractory asthma. Reproduced with permission from BMJ Publishing Group from Howarth et al.60 Journal of Allergy and Clinical Immunology 2006 117, 496-506DOI: (10.1016/j.jaci.2006.01.039) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 2 Domain structure of ADAM33 in relation to function. Each exon of the ADAM33 gene is identified by letters A through V (top). EGF, epidermal growth factor; UTR, untranslated region. Reprinted by permission from Macmillan Publishers Ltd: Van Eerdewegh et al.91 Journal of Allergy and Clinical Immunology 2006 117, 496-506DOI: (10.1016/j.jaci.2006.01.039) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 3 Localization of ADAM33 protein to airways smooth muscle (SM) in a bronchial biopsy specimen from a patient with severe asthma. Reprinted with permission from Haitchi et al.116 Official Journal of the American Thoracic Society. © American Thoracic Society. Journal of Allergy and Clinical Immunology 2006 117, 496-506DOI: (10.1016/j.jaci.2006.01.039) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 4 Alternatively spliced variants of ADAM33 in human fibroblasts identified by means of PCR. EGF, Epidermal growth factor; TM, transmembrane. Reprinted with permission from Powell et al.97 Official Journal of the American Thoracic Society. © American Thoracic Society. Journal of Allergy and Clinical Immunology 2006 117, 496-506DOI: (10.1016/j.jaci.2006.01.039) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 5 Three-dimensional structure of ADAM33 determined by means of crystallography in complex with the inhibitor Marimastat (shown as the stick and ball construct). The substrate binding site contains unique features that are specific for ADAM33, suggesting that it has a limited substrate specificity. C, C-terminal end; N, N-terminal end. Reprinted with permission from Orth et al.98 Journal of Allergy and Clinical Immunology 2006 117, 496-506DOI: (10.1016/j.jaci.2006.01.039) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 6 Immunolocalization of ADAM33 in 8- to 12-week human fetal lung tissue. ADAM33 immunoreactivity is mostly found around bronchial tubes in primitive mesenchymal cells but also in airways smooth muscle. αSMA, α Smooth muscle actin. Reprinted with permission from Haitchi et al.116 Official Journal of the American Thoracic Society. © American Thoracic Society. Journal of Allergy and Clinical Immunology 2006 117, 496-506DOI: (10.1016/j.jaci.2006.01.039) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions