World Allergy Forum Symposium: An Update on Severe Asthma - World

52 Pages·2008·4.18 MB·English

World Allergy Forum Symposium:
An Update on Severe Asthma
XXVII Congress of the European Academy of Allergology
and Clinical Immunology
Monday, 9 June 2008
15.30 – 17.00
Barcelona International Convention Centre
Room 211/212
Barcelona, Spain
Moderators:
G. Walter Canonica, Italy
Roy Gerth van Wijk, The Netherlands
The TENOR Study – the epidemiology of severe asthma
Eugene Bleecker, United States
Severe asthma – determinants and treatment
Klaus Rabe, The Netherlands
Four years’ experience of omalizumab – efficacy and safety
William Storms, United States
w w w. w o r l d a l l e r g y. o r g
Supported through an unrestricted educational grant from
The World Allergy Organization (WAO) is an international organization of 77 regional and national allergy and clinical immunology societies.
WAO’s mission is to be a global resource and advocate in the field of allergy, advancing excellence in clinical care, education, research and
training through a world-wide alliance of allergy and clinical immunology societies
WAF is an educational program of the World Allergy Organization

“An Update on Severe Asthma”
w w w. w o r l d a l l e r g y. o r g
Program
Moderators:
G. Walter Canonica
Italy

Roy Gerth van Wijk
The Netherlands
1. Welcome to the World Allergy Forum Symposium and Introduction to “An Update on
Severe Asthma”
G. Walter Canonica and Roy Gerth van Wijk
2. The TENOR Study – the epidemiology of severe asthma
Eugene Bleecker, United States
3. Severe asthma – determinants and treatment
Klaus Rabe, The Netherlands
4. Four years’ experience of omalizumab – efficacy and safety
William Storms, United States
2008-2009 World Allergy Form Advisory Board
Chair
G. Walter Canoncia, Italy
Vice Chair
Richard F. Lockey, United States
Core Advisors
Carlos Baena-Cagnani, Argentina
Jean Bousquet, France
Thomas B. Casale, United States
Roy Gerth van Wijk, The Netherlands
Stephen T. Holgate, United Kingdom
Michael A. Kaliner, United States
Ruby Pawankar, Japan
Advisors-at-Large
Takeshi Fukuda, Japan
Bee-Wah Lee, Singapore
Jorge Maspero, Argentina
Klaus Rabe, The Netherlands
Lanny Rosenwasser, United States
Pakit Vichyanond, Thailand

A W A o
bout the orld llergy rgAnizAtion
World Allergy orgAnizAtion (WAo)
The World Allergy Organization (WAO) is an international umbrella organization of 77 regional and national allergy and clinical
immunology societies. By collaborating with member societies, WAO provides direct educational outreach programs, symposia and
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the World Allergy orgAnizAtion Mission
To be a global resource and advocate in the field of allergy, advancing excellence in clinical
care through education, research and training as a world-wide alliance of allergy and clinical
immunology societies. w w w. w o r l d a l l e r g y. o r g
P W A o
rogrAMs of the orld llergy rgAnizAtion
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9 June 2008

Dear Colleagues,
World Allergy Forum has been honored to be part of the EAACI program for many years, and it is a great pleasure to bring
the 32nd World Allergy Forum symposium to the 2008 EAACI Congress, and to the beautiful city of Barcelona!
Our symposium today is an update on severe asthma; severe asthma is debilitating and frightening for patients, and one of
the major management challenges for allergists and pulmonologists. While our understanding of the immunopathology of
asthma has increased greatly over the years, until recently new treatment guidelines were able to offer little in the way of
advances in the pharmacotherapy of asthma, other than revised recommendations for the use of long-available treatments.
Eugene Bleecker will open today’s program by reporting on the US study into the Epidemiology and Natural History of
Asthma: Outcomes and Treatment Regimens (TENOR). We will hear the results of this 3-year, multicenter, observational
study of more than 4700 patients, aged 6 years or older, with severe or difficult-to-treat asthma. Klaus Rabe will then
discuss determinants and treatment of severe asthma. Concluding the symposium, William Storms will report on over four
years of experience with anti-IgE therapy in the treatment of chronic severe asthma. Information will be presented about the
safety and efficacy of the most recently introduced therapy for difficult-to-treat allergic asthma. We will hear that in clinical
practice, although patients reported improvements in all asthma parameters, this was not reflected by any change in FEV1,
a primary endpoint of so many research studies into asthma treatment efficacy.
We look forward to leading discussion with you on these exciting presentations!
With best regards,

G. Walter Canonica Roy Gerth Van Wijk
President President
World Allergy Organization European Academy of Allergology and Clinical Immunology


The Epidemiology of Severe Asthma: The TENOR Study and SARP (NIH)
Eugene R. Bleecker, MD
Thomas H. Davis Professor of Pulmonary Medicine
Section Head, Pulmonary, Critical Care, Allergy and Immunologic Diseases
Co-Director, Center for Human Genomics
Winston-Salem, NC
USA
“Severe Asthma” consists of up to 0% of asthma patients who asthma is common, representing a significant subset of asthmatics,
have frequent and severe symptoms despite aggressive therapy estimated at 0% of patients with asthma. In addition, these severe
with anti-inflammatory as well as other controller medications. asthmatics use disproportionately more healthcare resources.
They often have fixed and progressive reductions in pulmonary
The NIH (NHLBI) Severe Asthma Research Program (SARP) has
function that do not reverse completely either after intense acute or
characterized over 000 asthmatics of varying severity (and ~00
long-term therapy. These abnormalities in lung function may reflect
normal controls), including over 00 subjects with severe asthma.
structural changes in the airways that have been classified as
All subjects underwent detailed clinical, physiologic, inflammatory
“airway remodeling”. The varied clinical patterns found in severe
and in a subset, radiologic phenotyping. In addition, DNA from
asthma may reflect genetic differences that regulate bronchial
all SARP subjects is being genotyped using the Illumina  million
inflammation and interact with environmental stimuli resulting
SNP ship for Genome Wide Associations Studies (GWAS) analysis
in the characteristic pathophysiologic abnormalities as well as
as part of the NHLBI funded STAMPEED project. Investigative
propensity to airway remodeling. In addition, pharmacogenetic
bronchoscopies are routinely performed as part of each of the
responses may alter expected therapeutic responses and
independent SARP research projects.
influence asthma severity. Thus, it is important to understand and
characterize the clinical and inflammatory phenotyes in patients
While the NAEPP expert panel guidelines represent an important
with severe asthma. Specific disease patterns may emerge during
approach to classify asthma severity, the guidelines have well
this comprehensive phenotype evaluation (including biomarkers),
recognized problems which limit their use in clinical practice and
which would allow us to better understand the pathogenesis,
clinical research. For example, the need to classify severity of
development and treatment of more severe asthma.
patients when they are “off” medications is both impractical and,
for the severe of difficult-to-treat asthmatic, can be dangerous. In
The Epidemiology and Natural History of Asthma: Outcomes
addition, clinical investigators have recognized that asthmatics
and Treatment Regimes (TENOR) study was a two to three year
labeled “severe” can be characterized by several different clinical
multi-center observational cohort study of asthmatics described as
patterns of disease expression. In some patients, frequent and
“difficult to treat” by their physicians, sponsored by Genentech
severe symptoms occur despite aggressive therapy with anti-
and Novartis. It was not a clinical trial but rather a longitudinal
inflammatory as well as other controller medications. Other patients
cohort study of ,76 patients (% African American, 6.%
with asthma have fixed and progressive reductions in pulmonary
Hispanic, and .% Asian or Pacific Islanders) with asthma,
function that do not reverse completely either after intense acute
aged 6 or older, from 8 clinical centers including managed
or long-term therapy. These abnormalities in lung function may
care, HMO, community and academic centers. Subjects
reflect structural changes in the airways that have been classified
were included if they had physician-characterized difficult-to-
as “airway remodeling”.
treat asthma, and met additional criteria based on frequency
of urgent care visits and/or the use of multiple controller
The varied clinical patterns found in difficult-to-treat and severe
medications. In this group of asthmatics , .6% met the NHLBI
asthma almost certainly reflect genetic differences interacting with
National Asthma Education and Prevention Program (NAEPP)
environmental factors that regulate bronchial inflammation resulting
expert panel guidelines for severe persistent asthma, 7.%
in characteristic pathophysiologic abnormalities, the propensity for
for moderate persistent asthma, and 7.8% for mild persistent
airway remodeling, and different responses to asthma controller
asthma. All subjects were evaluated initially with comprehensive
therapy. Pharmacogenetic responses may be particularly important
questionnaires and laboratory testing, and were seen every 6
in these patients since the more difficult-to-treat asthma patients may
months during the remaining - years of the study. Detailed
not respond as well to controller therapies as do other asthmatics.
phenotypic information collected includes information on asthma
Thus, it is important to carefully define and characterize the
exacerbations, medication use, urgent care visits, quality of life,
phenotypic characteristics of difficult-to-treat and severe asthma in
pulmonary function tests (spirometry with reversibility), total serum
large population samples throughout the world.
IgE levels and history of allergies. Difficult-to-treat or severe

The Epidemiology of Severe Asthma: The TENOR Study and SARP (NIH)
References
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6
The Epidemiology of
Severe Asthma:
The TENOR Study and
SARP (NIH)
Professor Eugene R. Bleecker
Thomas H. Davis Professor of Medicine
Head, Pulmonary, Critical Care, Allergy
& Immunologic Diseases
Co-Director, Center for Human Genomics
Winston-Salem, NC
USA
Severe Asthma
• Asthma is a heterogeneous disease with
related clinical phenotypes
• Severe asthma represents 20% of total
asthma population and is difficult to treat
with high levels of morbidity, mortality and
health care costs.
Severe Asthma
• While progress has been made in
understanding the pathogenesis of
severe asthma, our understanding of
the complexity and heterogeneity of this
disorder remains limited
7
What is Severe Asthma:
A Tale of Two “Studies”?
•The Epidemiology and Natural
History of Asthma: Outcomes and
Treatment Regimes (TENOR)
•Severe Asthma Research Program
(SARP), NHLBI
TENOR Study Design
• 3-year, multi-center, observational study
- Patients continued to receive medications and
treatments administered for their asthma as indicated
by their physician
• 4,756 patients enrolled between January and October
2001
- aged 6 years or older
- 283 sites across the US
Dolan CM, Fraher KE, Bleecker ER, et al. Ann Allergy Asthma Immunol2004; 92:32-39
Objectives
• Primary objective
- Describe natural history of patients considered by
physicians to have “severe”or “difficult-to-treat”
asthma
• Secondary objectives
- Examine relationship between features of asthma,
treatments, and outcomes
- Observe frequency of comorbidconditions
- Examine the relationship between IgE and disease
IgE=Immunoglobulin E
8