Close
About
FAQ
Home
Collections
Login
USC Login
Register
0
Selected
Invert selection
Deselect all
Deselect all
Click here to refresh results
Click here to refresh results
USC
/
Digital Library
/
University of Southern California Dissertations and Theses
/
The effect of Omalizumab on free IgE and spirometric measurements in allergic asthmatics with highly elevated IgE levels
(USC Thesis Other)
The effect of Omalizumab on free IgE and spirometric measurements in allergic asthmatics with highly elevated IgE levels
PDF
Download
Share
Open document
Flip pages
Contact Us
Contact Us
Copy asset link
Request this asset
Transcript (if available)
Content
THE
EFFECT
OF
OMALIZUMAB
ON
FREE
IGE
AND
SPIROMETRIC
MEASUREMENTS
IN
ALLERGIC
ASTHMATICS
WITH
HIGHLY
ELEVATED
IGE
LEVELS
by
Sheila
M.
Bonilla
_________________________________________________________________________________________________
A
Thesis
Presented
to
the
FACULTY
OF
THE
USC
GRADUATE
SCHOOL
UNIVERSITY
OF
SOUTHERN
CALIFORNIA
In
Partial
Fulfillment
of
the
Requirements
for
the
Degree
MASTER
OF
SCIENCE
(CLINICAL
AND
BIOMEDICAL
INVESTIGATIONS)
May
2011
Copyright
2011
Sheila
M.
Bonilla
ii
DEDICATION
This
thesis
is
dedicated
to
my
husband,
Jose
S.
Tandoc,
III,
MD,
who
never
minded
being
called
Dr.
Bonilla
or
even
better,
Mr.
Bonilla.
He
will
always
be
my
pillar
no
matter
how
much
I
pretend
to
be
a
superwoman.
And
to
my
children,
Alec,
Noah
and
Katherine
who
always
manage
to
be
louder
than
a
cricket
but
always
make
me
feel
wanted
and
loved.
Thank
you.
iii
ACKNOWLEDGEMENTS
I
will
forever
thank
Dr.
Richard
Barbers,
for
taking
me
under
his
wing,
starting
me
off
in
this
research
study
and
guiding
me
into
becoming
a
mature
allergist
and
immunologist
that
I
have
become.
Dr.
Hooman
Allayee,
my
research
mentor
whose
critical
mind,
wit
and
guidance
made
this
thesis
possible.
Dr.
Stan
Azen,
a
mentor
to
all
but
genuinely
knows
how
to
make
me
feel
his
only
mentee.
Linda
Ehlig,
MSN,
my
allergy
nurse
who
assisted
me
in
treating
some
of
the
subjects.
And
to
all
my
co-‐authors
whose
names
would
appear
in
the
printed
publication.
Thank
you.
iv
TABLE
OF
CONTENTS
DEDICATION
ii
ACKNOWLEDGEMENTS
iii
LIST
OF
FIGURES
v
ABSTRACT
vi
INTRODUCTION
1
METHODS
STUDY
DESIGN
AND
POPULATION
STUDY
PROCEDURES
DATA
ANALYSIS
4
4
4
5
RESULTS
POPULATION
CHARACTERISTICS
TABLE
1.
BASELINE
CHARACTERISTICS
TOTAL
AND
FREE
IGE
LEVELS
AND
SPIROMETRIC
CHANGES
6
6
6
6
DISCUSSION
FUTURE
WORK
10
12
BIBLIOGRAPHY
13
ALPHABETIZED
BIBLIOGRAPHY
15
v
LIST
OF
FIGURES
Figure
1.
Total
IgE
Changes
Over
Time
8
Figure
2.
Free
IgE
Changes
Over
Time
8
Figure
3.
FEV1
Changes
Overt
Time
9
Figure
4.
Exhaled
Nitric
Oxide
Changes
Over
Time
9
vi
ABSTRACT
INTRODUCTION:
Omalizumab
has
been
shown
to
be
well
tolerated
and
effective
in
the
treatment
of
allergic
asthma
but
the
indication
is
limited
to
total
IgE
levels
of
up
to
700
kIU/L.
The
use
of
omalizumab
in
a
subgroup
of
allergic
asthmatics
with
highly
elevated
IgE
has
not
been
reported.
OBJECTIVE:
To
determine
whether
omalizumab
is
effective
in
reducing
free
IgE
levels
in
patients
with
total
IgE
levels
of
over
700
kIU/L
and
if
this
reduction
correlates
with
clinical
improvement
as
measured
by
spirometry.
METHODS:
A
pilot
study
of
8
patients
with
moderate
to
severe
asthma
and
an
elevated
IgE
levels
>1000
kIU/L
(+/-‐
100).
Omalizumab
was
given
subcutaneously
at
a
monthly
dosage
of
0.016mg/kg
x
total
IgE
level
divided
into
biweekly,
to
a
maximum
of
375
mg
per
dose.
Follow-‐up
was
done
every
six
months.
Six
of
8
patients
completed
6
months
with
free
IgE
level,
spirometry,
and
asthma
classification.
Another
2
patients
were
followed
over
2
years.
Exhaled
nitric
oxide
(eNO)
was
measured
in
one
patient
for
one
year.
RESULTS:
Total
IgE
levels
did
not
decrease
after
6
months
on
omalizumab
treatment
but
did
show
a
decreasing
trend
after
one
year.
A
similar
trend
was
seen
in
the
free
IgE
with
continued
decrease
after
2
years
in
2
patients.
Spirometric
values
were
not
affected
despite
clinical
improvement
based
on
decrease
in
systemic
steroid
use
and
decreasing
eNO
in
one
patient.
vii
CONCLUSIONS:
Moderate
to
severe
asthma
patients
with
high
serum
IgE
levels
of
over
>1000
kIU/L
showed
clinical
improvement
with
omalizumab
treatment
at
the
current
FDA
approved
dose
that
directly
correlates
with
reduced
free
IgE
levels
after
over
one
year
of
treatment.
1
INTRODUCTION
Allergic
bronchopulmonary
aspergillosis
(ABPA)
is
a
serious
respiratory
condition
which
is
characterized
by
chronic
airway
inflammation
and
damage
induced
by
persistent
colonization
and
sensitization
to
Aspergillus
species,
most
commonly
A.
fumigatus
(1)
.
Asthmatics
and
cystic
fibrosis
patients
with
excessive
mucus
and
impaired
clearance
may
be
more
susceptible
to
ABPA
as
inhaled
Aspergillus
spores
are
able
to
germinate
and
release
exoproteases
resulting
in
greater
antigen
adherence
and
absorption
(2,3)
.
Furthermore,
epithelium
activation
in
individuals
with
asthma
and
cystic
fibrosis
can
enhance
the
Aspergillus
penetration
of
bronchial
mucosa
(2)
.
This
provokes
a
cytokine
mediated
CD4+Th2
inflammatory
response
causing
eosinophilia,
increased
mucus
secretion
and
airway
remodeling.
These
patients
also
have
significantly
elevated
serum
IgE
levels
as
well
as
A.
fumigatus
specific
IgE,
IgG,
and
IgA
antibodies
furthering
immunological
reactions
(3,4)
.
Immunoglobulin
E
(IgE),
produced
by
B-‐cells
sensitized
to
allergens,
is
known
to
play
a
central
role
in
the
pathogenesis
of
various
allergic
conditions
including
asthma
and
rhinitis
(5)
.
During
an
exposure,
the
allergen
cross-‐links
IgE
molecules
on
the
mast
cells
and
basophils
initiating
degranulation
and
release
of
various
inflammatory
mediators
that
promote
airway
inflammation,
hypersensitivity
and
bronchospasm
(5,6)
.
2
Omalizumab
(Xolair),
a
recombinant
humanized
monoclonal
antibody,
binds
to
free
IgE
molecules
(7)
.
By
directly
reducing
circulating
IgE
levels,
omalizumab
in
turn
down-‐regulates
receptor
expression
on
effector
cells
over
time
(7,8)
.
Combination
of
these
effects
should
potentially
reduce
the
IgE-‐mediated
inflammatory
response
caused
by
various
allergens.
Indeed,
a
study
by
Djukanovic
et
al.
showed
decrease
in
free
IgE
and
FcεRI+
cells,
as
well
as
eosinophilia
in
patients
with
allergic
asthma
(9)
.
There
is
also
significant
improvement
in
forced
expiratory
volume
(FEV
1
)
seen
in
these
patients
after
allergen
challenge
(10)
.
There
are
four
major
randomized
double-‐blind
clinical
trials
that
have
compared
omalizumab
with
placebo
in
adults
with
allergic
asthma
(5,6)
.
The
results
consistently
showed
significant
fewer
exacerbations
and
hospitalization,
as
well
as
decreased
inhaled
steroid
requirements
amongst
patients
receiving
omalizumab
compared
to
placebo
group
(5:
Table2)
.
In
a
pooled
analysis
of
fourteen
trials,
Walker
et
al.
found
decreased
level
of
free
IgE
and
significant
reduction
in
daily
inhaled
steroid
use
(11)
.
Apart
from
the
clinical
efficacy
of
omalizumab
it
has
also
demonstrated
to
provide
notable
improvement
in
patients’
quality
of
life
(QoL).
In
a
meta-‐analysis,
Niebauer
et
al.
found
statistically
significant
QoL
benefits
as
measured
by
asthma-‐
specific
QoL
questionnaires
(AQLQ)
scores
(12)
.
Several
reports
have
also
shown
clinical
improvement
as
measured
by
FEV1
after
omalizumab
treatment
in
children
with
cystic
fibrosis
with
ABPA
(13,14,15)
.
Furthermore,
a
more
recent
study
showed
3
lowering
of
total
IgE
after
omalizumab
treatment
in
2
patients
with
ABPA
(16)
.
Omalizumab
has
also
been
shown
to
decrease
exhaled
nitric
oxide
(eNO),
a
measure
of
airway
inflammation
in
asthma
(17,
18)
.
Thus
it
appears
that
omalizumab,
as
an
anti-‐IgE
agent,
has
a
great
potential
in
not
only
treating
asthma,
but
also
many
other
allergic
diseases
where
IgE
plays
a
significant
role.
Here
we
describe
our
experience
with
omalizumab
in
8
patients
for
the
treatment
of
allergic
asthma
with
highly
elevated
IgE
levels.
4
METHODS
STUDY
DESIGN
AND
POPULATION
The
study
was
a
prospective,
open-‐label
pilot
study,
IRB
approved
to
recruit
up
to
12
patients.
Subjects
were
recruited
from
both
LAC-‐USC
Medical
Center
and
USC
Asthma
and
Allergy
Center.
Inclusion
criteria
included
evidence
of
reactive
airway
disease
based
on
forced
expiratory
volume
(FEV
1
)
improvement
of
>12%
following
beta-‐agonist
administration,
moderate
to
severe
persistent
asthma
for
at
least
one
year,
positive
skin
test
reaction
to
a
perennial
aeroallergen
and
high
IgE
levels
of
>
900
kIU/L.
Omalizumab
375
mg
was
given
subcutaneously
every
other
week.
All
patients
were
followed
every
6
months
for
the
study
but
followed
with
their
respective
allergists
and
pulmonologists
who
managed
their
asthma
care
separately
as
needed.
Patients
were
followed
for
a
year.
Continuation
of
omalizumab
was
assessed
after
initial
year.
STUDY
PROCEDURES
Studies
obtained
at
baseline
and
every
6
months
included
pulmonary
function
test
to
obtain
the
FEV
1
and
total
IgE
levels.
Free
IgE
levels
were
sent
to
Johns
Hopkins
Laboratory
6
months
after
initiation
of
omalizumab
then
every
6
months
therafter.
A
measurement
of
exhaled
nitric
oxide
was
later
added
to
the
study
once
the
apparatus
became
available
on-‐site.
5
DATA
ANALYSIS
Data
was
analyzed
using
paired
t-‐test,
comparing
baseline
data
to
six
months,
and
12
months,
24
months
and
36
months
if
available
on
the
same
patient.
6
RESULTS
POPULATION
CHARACTERISTICS
Eight
patients
met
the
criteria
and
were
recruited
to
participate.
Of
the
six
patients
who
were
able
to
complete
at
least
6
months
with
IgE
measurements
and
FEV
1
,
4
met
the
criteria
for
ABPA
(19)
.
Two
of
the
six
patients
were
able
to
follow
at
2
years
and
one
patient
at
3
years.
Only
one
patient
was
recruited
after
eNO
apparatus
became
available.
Table
1
outlines
baseline
characteristics
of
the
patients.
TABLE
1.
Baseline
Characteristics
Patient
ABPA
Baseline
Total
IgE
(klU/L)
Baseline
FEV1
Baseline
eNO
(ppb)
Patient
1
yes
5163
70%
Patient
2
no
3030
56%
Patient
3
no
910
61%
Patient
4
yes
13800
61%
Patient
7
yes
7600
86%
Patient
8
yes
4460
74%
48.5
TOTAL
AND
FREE
IGE
LEVELS
AND
FEV
1
VALUES
OVER
TIME
Figure
1
summarizes
the
total
IgE
levels
for
the
6
patients.
There
is
no
significant
decrease
in
the
total
IgE
nor
the
free
IgE
until
after
one
year
of
omalizumab
treatment.
On
the
contrary,
patient
2
and
3
who
both
did
not
meet
7
criteria
for
ABPA,
had
an
increase
of
their
total
IgE
after
6
months
of
treatment.
However,
both
total
IgE
and
free
IgE
seem
to
trend
down
at
2
years
and
3
years
(Figure
2).
Similarly,
FEV
1
did
not
show
any
significant
improvement
but
seemed
to
have
decreased
over
time,
as
well
(Figure
3).
All
patient
improved
clinically
based
on
no
systemic
steroids
use
or
hospitalizations
while
on
omalizumab.
Exhaled
nitric
oxide
decrease
over
time
in
patient
8
(Figure
4).
8
FIGURE
1.
Total
IgE
Changes
Over
Time
FIGURE
2.
Free
IgE
Changes
Over
Time
Total IgE Changes Over Time
0
2000
4000
6000
8000
10000
12000
14000
16000
0 6 12 24 36
Time in months
Total IgE (kIU/L)
Patient 1
Patient 2
Patient 3
Patient 4
Patient 7
Patient 8
Free IgE Changes Over Time
0
500
1000
1500
2000
2500
3000
3500
6 12 24 36
Time in months
Free IgE (kIU/L)
Patient 1
Patient 2
Patient 3
Patient 4
Patient 7
Patient 8
9
FIGURE
3.
FEV
1
Changes
Over
Time
FIGURE
4.
Exhaled
Nitric
Oxide
Over
Time
FEV1 Changes Over Time
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 6 12 24
Time in months
FEV1 as % predicted
Patient 1
Patient 2
Patient 3
Patient 4
Patient 7
Patient 8
Exhaled Nitric Oxide in Patient 8
0
10
20
30
40
50
60
0 6 12
Time in months
eNO in ppb
Patient 8
10
DISCUSSION
Our
data
shows
total
IgE
levels
to
be
unaffected
or
increased
at
6
months,
but
declines
after
one
year,
a
trend
that
was
also
seen
in
the
2
patients
presented
by
Lin
et
al
(16)
.
Similarly,
free
IgE
also
declined
after
one
year.
Elevation
of
total
IgE
at
the
initiation
of
omalizumab
therapy
in
patients
2
and
3
is
consistent
with
previous
reports
(20)
.
All
patients
did
well
clinically,
however,
without
any
hospitalizations
or
use
of
systemic
steroids
while
on
omalizumab
despite
no
change
in
their
FEV
1
.
This
lack
of
change
may
be
due
to
the
severity
of
baseline
bronchiectasis
and/or
insufficient
time
on
treatment.
We
hypothesized
that
omalizumab
would
bind
to
non-‐specific
free
IgE
including
specific
IgE
to
Aspergillus
and
thereby
would
lower
the
potential
immunological
reaction.
Stabilization
of
FEV
1
might
be
more
realistic
to
expect.
The
significance
of
free
IgE
as
it
relates
to
total
IgE
has
not
been
fully
understood.
We
used
skin
test
in
the
evaluation
of
perrenial
allergen.
It
would
be
interesting
to
find
out
in
the
patients
with
ABPA
which
particular
Aspergillus
they
are
sensitive
to.
Recent
study
by
Delhaes,
et
al,
showed
that
specific
IgE
to
different
recombinant
Aspergillus
may
be
related
to
the
severity
of
ABPA
in
patient
with
cystic
fibrosis
(21)
.
This
may
in
turn
relate
to
how
these
patients
respond
to
omalizumab.
11
Although
this
pilot
study
is
small,
our
data
suggest
that
omalizumab
may
have
potential
therapeutic
value
even
in
patients
with
very
high
IgE
and
severe
asthma,
with
or
without
ABPA.
This
is
clearly
seen
in
patient
8
as
reflected
by
the
significant
reduction
in
eNO.
Importantly,
the
reductions
we
observe
are
consistent
with
those
reported
in
patients
whose
IgE
levels
did
not
exceed
700
kIU/L,
a
reduction
which
can
be
as
much
as
over
90%
(22)
.
Future
studies
in
larger
numbers
of
patients
will
be
required
to
validate
these
preliminary
observations.
12
FUTURE
WORK
A
prospective,
open-‐label
trial
is
being
planned.
A
one-‐sided
test
hypothesis
predicting
at
least
a
50%
reduction
in
free
IgE
after
18
months
on
omalizumab
with
an
α
of
0.05
and
attrition
rate
of
30%
would
need
a
sample
size
of
36.
Baseline
data
will
include
free
IgE,
which
can
now
be
measured
by
a
commercial
laboratory.
As
this
pilot
study
did
not
show
any
effect
on
the
FEV1,
it
is
reasonable
to
add
a
quality
of
life
questionnaire
such
as
the
AQLQ
to
assess
clinical
significance.
Validation
of
specific
IgE
should
be
done
both
with
laboratory
testing
and
skin
testing.
Serum
should
ideally
be
stored
as
well
for
possible
genetic
testing
in
the
future.
13
BIBLIOGRAPHY
1. Gibson
PG.
Allergic
bronchopulmonary
aspergillosis.
Semin
Respir
Crit
Care
Med.
2006;27:185-‐91.
2. Tillie-‐Leblond,
Tonnel.
Allergic
bronchopulmonary
aspergillosis.
Allergy.
2005;60:1004-‐1013.
3. Virning
C,
Bush
RK.
Allergic
bronchopulmonary
aspergillosis:
a
US
perspective.
Curr
Opin
Pulm
Med.
2007;13:67-‐71.
4. Moss
RB.
Pathophysiology
and
immunology
of
allergic
bronchopulmonary
aspergillosis.
Med
Mycol.
2005;43:S203-‐6.
5. Nowak
D.
Management
of
asthma
with
anti-‐immunoglobulin
E:
A
review
of
clinical
trials
of
omalizumab.
Resp
Med.
2006;100:1907-‐1917.
6. Strunk
RC,
Bloomberg
GR.
Omalizumab
for
Asthma.
N
Eng
J
Med.
2006;354:2689-‐2695.
7. Soresi
S,
Togias
A.
Mechanisms
of
action
of
anti-‐immunoglobulin
E
therapy.
Allergy
&
Asthma
Proc.
2006;27:S15-‐23.
8. Saini
SS,
MacGlashan
Jr
DW,
Sterbinsky
SA,
et
al.
Down-‐regulation
of
human
basophil
IgE
and
FC
epsilon
RI
alpha
surface
densities
and
mediator
release
by
anti-‐IgE-‐infusions
in
reversible
in
vitro
and
in
vivo.
J
Immunol.
1999;162:5624-‐30.
9. Djukanovic
R,
Wilson
SJ,
et
al.
Effects
of
treatment
with
anti-‐immunoglobulin
E
antibody
omalizumab
on
airway
inflammation
in
allergic
asthma.
Am
J
Respir
Crit
Care
Med.
2004;170:583-‐93.
10. Fahy
JV,
Fleming
HE,
Wong
HH,
et
al.
The
effect
of
an
anti-‐IgE
monoclonal
antibody
on
the
early
and
late-‐phase
response
to
allergen
inhalation
in
asthmatic
subjects.
Am
J
Respir
Crit
Care
Med.
1997;155:1828-‐34.
11. Walker
S,
Monteil
M,
Phelan
K,
Lasserson
TJ,
Walter
EH.
Anti-‐IgE
for
chronic
asthma
in
adults
and
children.
Cochrane
Database
of
Systemic
Reviews
2004;3:CD003559.
12. Niebauer
K,
Dewilde
S,
Fox-‐Rushby
J,
Revicki
DA.
Impact
of
omalizumab
on
quality-‐of-‐life
outcomes
in
patients
with
moderate-‐to-‐severe
allergic
asthma.
Annals
of
Allergy,
Asthma,
&
Immunology.
2006;96:316-‐26.
14
13. Zirbes
JM,
Milla
CE.
Steroid-‐sparing
effect
of
omalizumab
for
allergic
bronchopulmonary
aspergillosis
and
cystic
fibrosis.
Pediatr
Pulmonol.
2008;43:607-‐10.
14. Kanu
A,
Patel
K.
Treatment
of
allergic
bronchopulmonary
aspergillosis
(ABPA)
in
CF
with
anti-‐IgE
antibody
(omalizumab).
Pediatr
Pulmonol.
2008;43:1249-‐51.
15. van
der
Ent
CK,
Hoekstra
H,
Rijkers
GT.
Successful
treatment
of
allergic
bronchopulmonary
aspergillosis
with
recombinant
anti-‐IgE
antibody.
Thorax.
2007;62:276-‐7.
16. Lin
RY,
Sethi
S,
Bhargave
GA.
Measured
Immunoglobulin
E
in
Allergic
Bronchopulmonary
Aspergillosis
Treated
with
Omalizumab.
J
Asthma.
2010;47:942-‐5.
17. Zietkowski
Z,
Skiepko
R,
Tomasiak-‐Lozowska
MM,
Lenczewska
D,
Bodzenta-‐
Lukaszyk
A.
RANTES
in
exhaled
breath
condensate
of
patients
with
severe
persistent
allergic
asthma
during
omalizumab
therapy.
Int
Arch
Allergy
Immunol.
2011;154:25-‐32.
18. Silkoff
PE,
Romero
FA,
Gupta
N,
Townley
RG,
Milgrom
H.
Exhaled
nitric
oxide
in
children
with
asthma
receiving
Xolair
(omalizumab),
a
monoclonal
anti-‐immunoglobulin
E
antibody.
Pediatrics.
2004;113:e308-‐12.
19. Patterson
R,
Greenberger
PA,
Radin
RC,
Roberts
M.
Allergic
bronchopulmonary
aspergillosis:
staging
as
an
aid
to
management.
Ann
Intern
Med.
1982;
96:286–291.
20.
Hayashi
N,
Tsukamoto
Y,
Sallas
WM,
Lowe
PJ.
A
mechanism-‐based
binding
model
for
the
population
pharmacokinetics
and
pharmacodynamics
of
omalizumab.
Br
J
Clin
Pharmacol.
2007;
63:548–561.
21. Delhaes
L,
Frealle
E,
Pinel
C.
Serum
markers
for
allergic
bronchopulmonary
aspergillosis
in
cystic
fibrosis:
State
of
the
art
and
further
challenges.
Med
Mycol.
2010;48:S77-‐87.
22. Corren
J,
Shapiro
G,
Reimann
J,
Deniz
Y,
Wong
D,
Adelman
D,
Togias
A.
Allergen
skin
tests
and
free
IgE
levels
during
reduction
and
cessation
of
omalizumab
therapy.
Allergy
Clin
Immunol.
2008;121:506-‐11.
15
ALPHABETIZED
BIBLIOGRAPHY
1. Corren
J,
Shapiro
G,
Reimann
J,
Deniz
Y,
Wong
D,
Adelman
D,
Togias
A.
Allergen
skin
tests
and
free
IgE
levels
during
reduction
and
cessation
of
omalizumab
therapy.
Allergy
Clin
Immunol.
2008;121:506-‐11.
2. Delhaes
L,
Frealle
E,
Pinel
C.
Serum
markers
for
allergic
bronchopulmonary
aspergillosis
in
cystic
fibrosis:
State
of
the
art
and
further
challenges.
Med
Mycol.
2010;48:S77-‐87.
3. Djukanovic
R,
Wilson
SJ,
et
al.
Effects
of
treatment
with
anti-‐immunoglobulin
E
antibody
omalizumab
on
airway
inflammation
in
allergic
asthma.
Am
J
Respir
Crit
Care
Med.
2004;170:583-‐93.
4. Fahy
JV,
Fleming
HE,
Wong
HH,
et
al.
The
effect
of
an
anti-‐IgE
monoclonal
antibody
on
the
early
and
late-‐phase
response
to
allergen
inhalation
in
asthmatic
subjects.
Am
J
Respir
Crit
Care
Med.
1997;155:1828-‐34.
5. Gibson
PG.
Allergic
bronchopulmonary
aspergillosis.
Semin
Respir
Crit
Care
Med.
2006;27:185-‐91.
6. Hayashi
N,
Tsukamoto
Y,
Sallas
WM,
Lowe
PJ.
A
mechanism-‐based
binding
model
for
the
population
pharmacokinetics
and
pharmacodynamics
of
omalizumab.
Br
J
Clin
Pharmacol.
2007;
63:548–561.
7. Kanu
A,
Patel
K.
Treatment
of
allergic
bronchopulmonary
aspergillosis
(ABPA)
in
CF
with
anti-‐IgE
antibody
(omalizumab).
Pediatr
Pulmonol.
2008;43:1249-‐51.
8. Lin
RY,
Sethi
S,
Bhargave
GA.
Measured
Immunoglobulin
E
in
Allergic
Bronchopulmonary
Aspergillosis
Treated
with
Omalizumab.
J
Asthma.
2010;47:942-‐5.
9. Moss
RB.
Pathophysiology
and
immunology
of
allergic
bronchopulmonary
aspergillosis.
Med
Mycol.
2005;43:S203-‐6.
10. Niebauer
K,
Dewilde
S,
Fox-‐Rushby
J,
Revicki
DA.
Impact
of
omalizumab
on
quality-‐of-‐life
outcomes
in
patients
with
moderate-‐to-‐severe
allergic
asthma.
Annals
of
Allergy,
Asthma,
&
Immunology.
2006;96:316-‐26.
11. Nowak
D.
Management
of
asthma
with
anti-‐immunoglobulin
E:
A
review
of
clinical
trials
of
omalizumab.
Resp
Med.
2006;100:1907-‐1917.
16
12. Patterson
R,
Greenberger
PA,
Radin
RC,
Roberts
M.
Allergic
bronchopulmonary
aspergillosis:
staging
as
an
aid
to
management.
Ann
Intern
Med.
1982;
96:286–291.
13. Saini
SS,
MacGlashan
Jr
DW,
Sterbinsky
SA,
et
al.
Down-‐regulation
of
human
basophil
IgE
and
FC
epsilon
RI
alpha
surface
densities
and
mediator
release
by
anti-‐IgE-‐infusions
in
reversible
in
vitro
and
in
vivo.
J
Immunol.
1999;162:5624-‐30.
14. Silkoff
PE,
Romero
FA,
Gupta
N,
Townley
RG,
Milgrom
H.
Exhaled
nitric
oxide
in
children
with
asthma
receiving
Xolair
(omalizumab),
a
monoclonal
anti-‐immunoglobulin
E
antibody.
Pediatrics.
2004;113:e308-‐12.
15. Soresi
S,
Togias
A.
Mechanisms
of
action
of
anti-‐immunoglobulin
E
therapy.
Allergy
&
Asthma
Proc.
2006;27:S15-‐23.
16. Strunk
RC,
Bloomberg
GR.
Omalizumab
for
Asthma.
N
Eng
J
Med.
2006;354:2689-‐2695.
17. Tillie-‐Leblond,
Tonnel.
Allergic
bronchopulmonary
aspergillosis.
Allergy.
2005;60:1004-‐1013.
18. van
der
Ent
CK,
Hoekstra
H,
Rijkers
GT.
Successful
treatment
of
allergic
bronchopulmonary
aspergillosis
with
recombinant
anti-‐IgE
antibody.
Thorax.
2007;62:276-‐7.
19. Virning
C,
Bush
RK.
Allergic
bronchopulmonary
aspergillosis:
a
US
perspective.
Curr
Opin
Pulm
Med.
2007;13:67-‐71.
20. Walker
S,
Monteil
M,
Phelan
K,
Lasserson
TJ,
Walter
EH.
Anti-‐IgE
for
chronic
asthma
in
adults
and
children.
Cochrane
Database
of
Systemic
Reviews
2004;3:CD003559.
21. Zietkowski
Z,
Skiepko
R,
Tomasiak-‐Lozowska
MM,
Lenczewska
D,
Bodzenta-‐
Lukaszyk
A.
RANTES
in
exhaled
breath
condensate
of
patients
with
severe
persistent
allergic
asthma
during
omalizumab
therapy.
Int
Arch
Allergy
Immunol.
2011;154:25-‐32.
22. Zirbes
JM,
Milla
CE.
Steroid-‐sparing
effect
of
omalizumab
for
allergic
bronchopulmonary
aspergillosis
and
cystic
fibrosis.
Pediatr
Pulmonol.
2008;43:607-‐10.
Abstract (if available)
Linked assets
University of Southern California Dissertations and Theses
Conceptually similar
PDF
Clinical outcomes of allogeneic hematopoietic stem cell transplant in acute lymphoblastic leukemia patients: a quality improvement project and systematic review meta-analysis
PDF
Induction therapy in relapse adult acute lymphoblastic leukemia
PDF
Effect of soy isoflavones on anthropometric and metabolic measurements in postmenopausal women
PDF
The Filipino family initiative: preliminary effects of an evidence-based parenting intervention offered in churches on parent and child outcomes
PDF
An assessment of impact of early local progression on subsequent risk for the treatment failure in adolescent and young adult patients with non-metastatic osteosarcoma
PDF
Assessing the utility of wearable fitness trackers for objective capture and quantification of activity levels among patients undergoing radical cystectomy
PDF
Effects of testosterone and growth hormone supplementation therapies on quality of life in older men: exploratory findings from the HORMA study
PDF
Comparison of secondary and primary thyroid cancer in adolescents and young adults (AYA)
PDF
The effect of cytomegalovirus on gene expression of pediatric acute lymphoblastic leukemia
PDF
A pilot study of chemotherapy intensification by adding vincristine, topotecan and cyclophosphamide to standard chemotherapy agents with an interval compression schedule in newly diagnosed patien...
PDF
Comparative biomolecular and therapeutic effectiveness of collaborative integrative intervention in morbidly obese individuals
PDF
The pharmacokinetics and pharmacodynamics of vincristine in the adolescent and young adult population compared to younger patients
PDF
Effects of protease inhibitor use on combined oral contraceptive pharmacokinetics and pharmacodynamics in HIV-positive women
PDF
The impact of treatment decisions and adherence on outcomes in small hereditary disease populations
PDF
Effects of post-menopausal hormone therapy on arterial stiffness in the ELITE trial
PDF
Linking air pollution to integrative gene and metabolites networks in young adult with asthma
PDF
The evaluation of the long-term effectiveness of zero/low fluoroscopy workflow in ablation procedures for the treatment of paroxysmal and persistent atrial fibrillation
PDF
Age related macular degeneration in Latinos: risk factors and impact on quality of life
Asset Metadata
Creator
Bonilla, Sheila M.
(author)
Core Title
The effect of Omalizumab on free IgE and spirometric measurements in allergic asthmatics with highly elevated IgE levels
School
Keck School of Medicine
Degree
Master of Science
Degree Program
Clinical and Biomedical Investigations
Publication Date
04/14/2011
Defense Date
04/11/2011
Publisher
University of Southern California
(original),
University of Southern California. Libraries
(digital)
Tag
ABPA,aspergillosis,asthma,IgE,OAI-PMH Harvest,omalizumab
Language
English
Contributor
Electronically uploaded by the author
(provenance)
Advisor
Allayee, Hooman (
committee chair
), Barbers, Richard (
committee chair
), Azen, Stanley Paul (
committee member
)
Creator Email
sbonilla@usc.edu,sheilabonilla@gmail.com
Permanent Link (DOI)
https://doi.org/10.25549/usctheses-m3747
Unique identifier
UC1279973
Identifier
etd-Bonilla-4491 (filename),usctheses-m40 (legacy collection record id),usctheses-c127-441538 (legacy record id),usctheses-m3747 (legacy record id)
Legacy Identifier
etd-Bonilla-4491.pdf
Dmrecord
441538
Document Type
Thesis
Rights
Bonilla, Sheila M.
Type
texts
Source
University of Southern California
(contributing entity),
University of Southern California Dissertations and Theses
(collection)
Repository Name
Libraries, University of Southern California
Repository Location
Los Angeles, California
Repository Email
cisadmin@lib.usc.edu
Tags
ABPA
aspergillosis
IgE
omalizumab