dreamchaser
New member
<i>I thought some of you may be interested in this, although i realise it is only one case i found it particularly interesting. I know some of you already take Xolair and im would be interested why you take it (not all of you take it for asp.), how often you take it and if it was your docs idea? </i>
It is from the medical journal Thorax
****
CAS E R E P ORT
Successful treatment of allergic bronchopulmonary
aspergillosis with recombinant anti-IgE antibody
Cornelis K van der Ent, Hans Hoekstra, Ger T Rijkers
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
T<b>horax 2007;62:276 - 277. doi: 10.1136/thx.2004.035519
Allergic bronchopulmonary aspergillosis (ABPA) can cause
severe worsening of the respiratory condition in patients with
cystic fibrosis. Treatment can result in steroid dependency and
serious adverse events. A dramatic and rapid improvement of
respiratory symptoms and lung function after a single dose of
anti-IgE antibody (omalizumab) in a 12-year-old girl with cystic
fibrosis and ABPA is described. This is the first report of this
experimental treatment. It suggests an important role for IgE in
t he pat hogenesi s of ABPA and of f ers new t herapeut i c
possibilities.
A
llergic bronchopulmonary aspergillosis (ABPA) occurs in
up to 15% of patients with cystic fibrosis.
1
Clinically, the
disease is manifested by wheezing, pulmonary infiltrates
and bronchiectasis. A number of immunological responses to
antigens of Aspergillus fumigatus can be observed, such as
peripheral blood eosinophilia, immediate cutaneous reactivity,
increased levels of total serum IgE, the presence of precipitating
antibodies and increased specific serum IgE and IgG antibodies
to A fumigatus.
1
Treatment for ABPA involves attenuation of the
inflammatory and immunological activity with corticosteroids
and reduction of the antigen burden from fungal colonisation
with antifungal agents. Long-term treatment is often required
because of exacerbations that repeatedly occur when cortico-
steroid treatment has been tapered. Serious adverse events to
corticosteroids are frequent in these patients. In this report, we
successfully treated a patient with recombinant anti-IgE
antibody (omalizumab). </b>
C A S E H I S T O R Y
A 12-year-old girl had been diagnosed with cystic fibrosis
directly after birth because of meconium ileum (genotype
dF508/dF508). From infancy she had mild to moderate lung
problems requiring antibiotic treatment three to five times a
year. From age 5 years she was colonised with Pseudomonas
aeruginosa and A fumigatus. At age 8 years she had more severe
signs of cough and exercise-induced asthma. She developed
pulmonary infiltrates and bronchiectasis and signs of severe
airflow obstruction (forced expiratory volume in 1 s (FEV1) fell
from 105% to 34% of predicted). Blood testing revealed
eosinophilia, marked increase in total serum IgE level
(5200 IU/ml), positive Aspergillus-specific IgE-radio allergosor-
bent test (class 4 - 5) and positive precipitating IgG antibodies to
Aspergillus. The diagnosis of ABPA was made and corticosteroids
were started (prednisone 50 mg/day). Within several days, her
symptoms disappeared and the lung function parameters
returned to normal. The corticosteroids could be tapered after
3 weeks. Between ages 8 and 12 years, exacerbations of ABPA
recurred many times when the dosage of prednisone was
reduced below 10 - 15 mg/day. Prednisone could not be
stopped. At 12 years of age, she developed the complete
spectrum of severe corticosteroid-related adverse events
(growth retardation, adiposity, hypertension and osteoporosis).
For this reason, we considered an alternative treatment
strategy - namely, treatment with omalizumab. After cessation
of the corticosteroids her FEV1 fell from 105% to 65% of
predicted in 2.5 weeks time (fig 1). Subcutaneous administra-
tion of a single dose of 300 mg omalizumab resulted in
complete disappearance of complaints of dyspnoea and an
increase in FEV1 to 98% of predicted within 4 h. After 2 weeks
her lung function began to decline again. FEV1 was 64% of
predicted 18 days after the first dose, and a second dose of
omalizumab was given. The same clinical results were observed
repeatedly in the period thereafter (fig 1). To date, the patient is
free of corticosteroids and doing well clinically. During the
treatment period no changes in total or specific immunoglo-
bulins (IgE, IgG and IgA) were observed. However, omalizumab
can interfere with accurate quantitation of serum IgE levels as a
result of omalizumab - IgE binding. During treatment no clinical
detectable adverse effects were observed.
D I S C U S S I O N
To our knowledge, this is the first patient with cystic fibrosis
with ABPA to be treated with omalizumab. There was a
repeated improvement in symptoms and normalisation of lung
function within 2 - 4 h of administration of the drug. Several
lessons can be drawn from this observation.
Omalizumab improves asthma control in patients with severe
allergic asthma, reducing inhaled corticosteroid requirements.
2
Although in patients with asthma the exacerbation rate
declines during treatment, the effects on lung function remain
relatively small. The dramatic improvement in both respiratory
symptoms and FEV1 in our patient suggests that omalizumab
might offer a new therapeutic approach to patients with ABPA.
Of course, our unblinded observations are not ultimate proof of
the efficacy of omalizumab in ABPA. However, the striking,
consistent and repeatable effects of subsequent administrations
120
100
80
60
40
- 9 - 6 - 3 0 3 6
Time (weeks)
Omalizumab
FVC
FEV1
Stop prednisone
Pe
rc
en
ta
g
e
p
re
d
ic
te
d
Figure 1 Lung function parameters (forced vital capacity (FVC) and forced
expiratory volume in 1 s (FEV1), expressed as percentages of predicted)
before and after treatment with omalizumab.
www.thoraxjnl.com
indicate effectiveness in our patient and justify future
randomised clinical trials.
The pathogenesis of ABPA remains complex and confusing.
In all patients, very high total serum IgE levels and high levels
of IgE anti-Aspergillus antibodies are seen. There seem to be
quantitative and perhaps qualitative differences in the B cell
IgE antibody responses between those with ABPA and those
without ABPA.
3
In ABPA, there are also increased amounts of
IgG and IgA anti-Aspergillus antibodies, which reflect the
balance between T helper cells types 2 and 1 in the response
to Aspergillus antigens in these patients.
4
To date, it has not been
clear whether extreme amounts of IgE play a role in the
pathogenesis of ABPA or whether it is only an epiphenomenon.
The timing of the effects after administration of omalizumab in
our patient suggests that IgE antibody might have an important
role in the signs of airflow obstruction in ABPA. The serum
levels of free IgE are reduced in a dose-dependent manner
within 2 h of subcutaneous administration of omalizumab. The
half-life of the drug in serum is about 22 days.
5
In our patient,
clinical improvement was observed within several hours,
lasting for 2 - 3 weeks.
The diagnosis of ABPA in cystic fibrosis is difficult because
many of the diagnostic criteria overlap with common manifes-
tations of cystic fibrosis. The diagnosis is based on the presence
of five or more essential criteria as proposed by the interna-
tional consensus committees,
1
and specific tests are lacking.
When our observation is confirmed in other patients, the rapid
and clear improvement of clinical signs and lung function after
a single dose of omalizumab might be used as a helpful
diagnostic test for ABPA.
Authors' affiliations
Cornelis K van der Ent, Department of Pediatric Respiratory Diseases,
University Medical Center Utrecht, Utrecht, The Netherlands
Hans Hoekstra, Department of Pediatrics, Hieronymus Bosch Hospital,
Hertogenbosch, The Netherlands
Ger T Rijkers, Department of Pediatric Immunology, University Medical
Center Utrecht, Utrecht, The Netherlands
Funding: None.
Competing interests: None.
Correspondence to: Dr C K van der Ent, Department of Pediatric
Respiratory Diseases, University Medical Center Utrecht, KH 01.419.0, PO
Box 85090, 3508 AB Utrecht, The Netherlands; k.vanderent@wkz.azu.nl
Received 30 September 2004
Accepted 17 January 2005
RE F E RE NCE S
1 Stevens DA, Moss RB, Kurup VP, and participants in the Cystic Fibrosis
Foundation Consensus Conference, et al. Allergic bronchopulmonary
aspergillosis in cystic fibrosis - state of the art: Cystic Fibrosis Foundation
Consensus Conference. Clin Infect Dis 2003;37(Suppl 3):S225 - 64.
2 Holgate ST, Chuchalin AG, Hebert J, et al. Efficacy and safety of a recombinant
anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma. Clin
Exp Allergy 2004;34:632 - 8.
3 El Dahr JM, Fink R, Selden R, et al. Development of immune responses to
Aspergillus at an early age in children with cystic fibrosis. Am J Respir Crit Care
Med 1994;150:1513 - 18.
4 Leser C, Kaufmann HF, Virchow C Sr, et al. Specific serum immunopatterns in
clinical phases of allergic bronchopulmonary aspergillosis. J Allergy Clin
Immunol 1992;90:589 - 99.
5 Hochhaus G, Brookman L, Fox H, et al. Pharmacodynamics of omalizumab:
implications for optimised dosing strategies and clinical efficacy in the treatment
of allergic asthma. Curr Med Res Opin 2003;19:491 - 8.
It is from the medical journal Thorax
****
CAS E R E P ORT
Successful treatment of allergic bronchopulmonary
aspergillosis with recombinant anti-IgE antibody
Cornelis K van der Ent, Hans Hoekstra, Ger T Rijkers
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
T<b>horax 2007;62:276 - 277. doi: 10.1136/thx.2004.035519
Allergic bronchopulmonary aspergillosis (ABPA) can cause
severe worsening of the respiratory condition in patients with
cystic fibrosis. Treatment can result in steroid dependency and
serious adverse events. A dramatic and rapid improvement of
respiratory symptoms and lung function after a single dose of
anti-IgE antibody (omalizumab) in a 12-year-old girl with cystic
fibrosis and ABPA is described. This is the first report of this
experimental treatment. It suggests an important role for IgE in
t he pat hogenesi s of ABPA and of f ers new t herapeut i c
possibilities.
A
llergic bronchopulmonary aspergillosis (ABPA) occurs in
up to 15% of patients with cystic fibrosis.
1
Clinically, the
disease is manifested by wheezing, pulmonary infiltrates
and bronchiectasis. A number of immunological responses to
antigens of Aspergillus fumigatus can be observed, such as
peripheral blood eosinophilia, immediate cutaneous reactivity,
increased levels of total serum IgE, the presence of precipitating
antibodies and increased specific serum IgE and IgG antibodies
to A fumigatus.
1
Treatment for ABPA involves attenuation of the
inflammatory and immunological activity with corticosteroids
and reduction of the antigen burden from fungal colonisation
with antifungal agents. Long-term treatment is often required
because of exacerbations that repeatedly occur when cortico-
steroid treatment has been tapered. Serious adverse events to
corticosteroids are frequent in these patients. In this report, we
successfully treated a patient with recombinant anti-IgE
antibody (omalizumab). </b>
C A S E H I S T O R Y
A 12-year-old girl had been diagnosed with cystic fibrosis
directly after birth because of meconium ileum (genotype
dF508/dF508). From infancy she had mild to moderate lung
problems requiring antibiotic treatment three to five times a
year. From age 5 years she was colonised with Pseudomonas
aeruginosa and A fumigatus. At age 8 years she had more severe
signs of cough and exercise-induced asthma. She developed
pulmonary infiltrates and bronchiectasis and signs of severe
airflow obstruction (forced expiratory volume in 1 s (FEV1) fell
from 105% to 34% of predicted). Blood testing revealed
eosinophilia, marked increase in total serum IgE level
(5200 IU/ml), positive Aspergillus-specific IgE-radio allergosor-
bent test (class 4 - 5) and positive precipitating IgG antibodies to
Aspergillus. The diagnosis of ABPA was made and corticosteroids
were started (prednisone 50 mg/day). Within several days, her
symptoms disappeared and the lung function parameters
returned to normal. The corticosteroids could be tapered after
3 weeks. Between ages 8 and 12 years, exacerbations of ABPA
recurred many times when the dosage of prednisone was
reduced below 10 - 15 mg/day. Prednisone could not be
stopped. At 12 years of age, she developed the complete
spectrum of severe corticosteroid-related adverse events
(growth retardation, adiposity, hypertension and osteoporosis).
For this reason, we considered an alternative treatment
strategy - namely, treatment with omalizumab. After cessation
of the corticosteroids her FEV1 fell from 105% to 65% of
predicted in 2.5 weeks time (fig 1). Subcutaneous administra-
tion of a single dose of 300 mg omalizumab resulted in
complete disappearance of complaints of dyspnoea and an
increase in FEV1 to 98% of predicted within 4 h. After 2 weeks
her lung function began to decline again. FEV1 was 64% of
predicted 18 days after the first dose, and a second dose of
omalizumab was given. The same clinical results were observed
repeatedly in the period thereafter (fig 1). To date, the patient is
free of corticosteroids and doing well clinically. During the
treatment period no changes in total or specific immunoglo-
bulins (IgE, IgG and IgA) were observed. However, omalizumab
can interfere with accurate quantitation of serum IgE levels as a
result of omalizumab - IgE binding. During treatment no clinical
detectable adverse effects were observed.
D I S C U S S I O N
To our knowledge, this is the first patient with cystic fibrosis
with ABPA to be treated with omalizumab. There was a
repeated improvement in symptoms and normalisation of lung
function within 2 - 4 h of administration of the drug. Several
lessons can be drawn from this observation.
Omalizumab improves asthma control in patients with severe
allergic asthma, reducing inhaled corticosteroid requirements.
2
Although in patients with asthma the exacerbation rate
declines during treatment, the effects on lung function remain
relatively small. The dramatic improvement in both respiratory
symptoms and FEV1 in our patient suggests that omalizumab
might offer a new therapeutic approach to patients with ABPA.
Of course, our unblinded observations are not ultimate proof of
the efficacy of omalizumab in ABPA. However, the striking,
consistent and repeatable effects of subsequent administrations
120
100
80
60
40
- 9 - 6 - 3 0 3 6
Time (weeks)
Omalizumab
FVC
FEV1
Stop prednisone
Pe
rc
en
ta
g
e
p
re
d
ic
te
d
Figure 1 Lung function parameters (forced vital capacity (FVC) and forced
expiratory volume in 1 s (FEV1), expressed as percentages of predicted)
before and after treatment with omalizumab.
www.thoraxjnl.com
indicate effectiveness in our patient and justify future
randomised clinical trials.
The pathogenesis of ABPA remains complex and confusing.
In all patients, very high total serum IgE levels and high levels
of IgE anti-Aspergillus antibodies are seen. There seem to be
quantitative and perhaps qualitative differences in the B cell
IgE antibody responses between those with ABPA and those
without ABPA.
3
In ABPA, there are also increased amounts of
IgG and IgA anti-Aspergillus antibodies, which reflect the
balance between T helper cells types 2 and 1 in the response
to Aspergillus antigens in these patients.
4
To date, it has not been
clear whether extreme amounts of IgE play a role in the
pathogenesis of ABPA or whether it is only an epiphenomenon.
The timing of the effects after administration of omalizumab in
our patient suggests that IgE antibody might have an important
role in the signs of airflow obstruction in ABPA. The serum
levels of free IgE are reduced in a dose-dependent manner
within 2 h of subcutaneous administration of omalizumab. The
half-life of the drug in serum is about 22 days.
5
In our patient,
clinical improvement was observed within several hours,
lasting for 2 - 3 weeks.
The diagnosis of ABPA in cystic fibrosis is difficult because
many of the diagnostic criteria overlap with common manifes-
tations of cystic fibrosis. The diagnosis is based on the presence
of five or more essential criteria as proposed by the interna-
tional consensus committees,
1
and specific tests are lacking.
When our observation is confirmed in other patients, the rapid
and clear improvement of clinical signs and lung function after
a single dose of omalizumab might be used as a helpful
diagnostic test for ABPA.
Authors' affiliations
Cornelis K van der Ent, Department of Pediatric Respiratory Diseases,
University Medical Center Utrecht, Utrecht, The Netherlands
Hans Hoekstra, Department of Pediatrics, Hieronymus Bosch Hospital,
Hertogenbosch, The Netherlands
Ger T Rijkers, Department of Pediatric Immunology, University Medical
Center Utrecht, Utrecht, The Netherlands
Funding: None.
Competing interests: None.
Correspondence to: Dr C K van der Ent, Department of Pediatric
Respiratory Diseases, University Medical Center Utrecht, KH 01.419.0, PO
Box 85090, 3508 AB Utrecht, The Netherlands; k.vanderent@wkz.azu.nl
Received 30 September 2004
Accepted 17 January 2005
RE F E RE NCE S
1 Stevens DA, Moss RB, Kurup VP, and participants in the Cystic Fibrosis
Foundation Consensus Conference, et al. Allergic bronchopulmonary
aspergillosis in cystic fibrosis - state of the art: Cystic Fibrosis Foundation
Consensus Conference. Clin Infect Dis 2003;37(Suppl 3):S225 - 64.
2 Holgate ST, Chuchalin AG, Hebert J, et al. Efficacy and safety of a recombinant
anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma. Clin
Exp Allergy 2004;34:632 - 8.
3 El Dahr JM, Fink R, Selden R, et al. Development of immune responses to
Aspergillus at an early age in children with cystic fibrosis. Am J Respir Crit Care
Med 1994;150:1513 - 18.
4 Leser C, Kaufmann HF, Virchow C Sr, et al. Specific serum immunopatterns in
clinical phases of allergic bronchopulmonary aspergillosis. J Allergy Clin
Immunol 1992;90:589 - 99.
5 Hochhaus G, Brookman L, Fox H, et al. Pharmacodynamics of omalizumab:
implications for optimised dosing strategies and clinical efficacy in the treatment
of allergic asthma. Curr Med Res Opin 2003;19:491 - 8.