ALLERGY VACCINE IMMUNOTHERAPY IN MANAGING ASTHMA

ALLERGY VACCINE IMMUNOTHERAPY IN MANAGING ASTHMA

Mark Greenwald

Department of Pediatrics, University of Toronto; Allergy Canada Ltd.

Corresponding Author: dmarkgreenwald@rogers.com


ABSTRACT

Current pharmacological treatment of asthma is effective at controlling many disease parameters but has not
been shown to have an impact on the basic pathological mechanisms. Allergy plays a major role in asthma
and allergy vaccine immunotherapy is a treatment that can modify allergic disease. The basis for using
allergy vaccine immunotherapy in asthma is explored.

Key Words: Immunotherapy, asthma treatment, allergic asthma, allergy vaccine


sthma is an inflammatory disease and current
natural progress of allergic rhinitis to asthma.4 IT
be
A st management aims to reduce the provides the potential to down-regulate this
inflammation already present and curtail exposure
inflammatory cascade, reduce IgE antibody
to pro-inflammatory agents. Some examples
production, and attenuate symptoms.5,6
include the use of corticosteroids and Conceptually, early intervention for allergic
antileukotrienes, avoiding cats and reducing
disease holds the most promise as therapeutic
exposure to dust mites. There is ongoing research
intervention capable of arresting the progression
to establish the evidence base for these
of the disease, altering the severity of the disease,
recommendations.
and/or preventing the evolution of allergic upper

The cause of asthma inflammation is in most
respiratory disease into asthma.7
cases allergy; an inappropriate immunological

Ross, Nelson and Feingold reviewed all
reaction. Therapy aimed to normalize the
English language studies of IT in asthma between
immunology is likely to actively alter the natural
1966 and 1998.8 All prospective, randomized,
course of this and other allergic disorders. The
double-blind, placebo-controlled studies of IT
World Health Organization very recently defined
were included in this meta-analysis.
allergen immunotherapy (IT), known at various
Immunotherapy was judged effective in 71% and
times as desensitization or hyposensitization, as
ineffective in 17% (P=0.0005). IT was more likely
‘therapeutic vaccines for allergic diseases’.1 Why
to improve symptoms (OR 2.76, 95% CI 2.22 to
then is there such reluctance to use allergy vaccine
3.42), reduce the need for medications (OR 2.00,
immunotherapy in the treatment of asthma? The
95% CI 1.46 to 2.72), improve pulmonary
recommendations of professional bodies and
function (OR 2.87, 95% CI 1.82 to 4.52), and
individual doctors in Canada have ranged from
protect against bronchial challenge (OR 1.81, 95%
very cautious acceptance to outright dismissal.
CI 1.32 to 2.49). Most studies were able to

Allergy vaccine immunotherapy is clinically
demonstrate a significant positive treatment effect
effective.2, 3 Use of insect venoms has saved lives.
even though the studies were heterogeneous with
Improvement has been demonstrated in clinical
respect to the selection of subjects, the underlying
symptoms, skin reactivity and medication scores
populations, the main treatment protocol, the
for allergy induced by grass, ragweed and tree
quality and amount of extracts used, the
pollen, animal hair and dander, house dust mite
concomitant treatments and the duration of
and mould. Allergy vaccine immunotherapy
treatment and follow-up.
inhibits new sensitization in monosensitized

Sigman and Mazer reviewed the 12 studies
children and prevents or decreases the rate of the
on IT in childhood asthma performed between
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Allergy vaccine immunotherapy in managing asthma
1966 and 1994.9 Eight were double-blinded and
two reasons allergy vaccine immunotherapy is not
most studies were 1 year or longer in duration.
being used more today are: 1) that the art and
Seventy five percent of the studies utilized
science have been forgotten and are not being
symptom recording. Changes in bronchial taught widely enough; and that 2) the application
hypereactivity were measured in 50% and
of evidence based medicine17,18 is weaker than the
medication usage in 25%. The antigens used
inherited bias against allergy vaccine
varied widely. Two studies showed significant
immunotherapy in general, and for asthma
improvement in bronchial hyper-responsiveness.
specifically.
In one study there was a decrease in symptom

scores (P<0.05) and drug scores in the first year
REFERENCES
(P= 0.007), in another there was a loss of the late
1. Bousquet J, Lockey RF, Malling H-J, WHO
asthmatic response upon bronchial provocation to
Position Paper. Allergen immunotherapy:
house dust mite (D. pteronyssinus) after 1 year of
therapeutic vaccines for allergic diseases. Allergy
1998;53:(44), 1-43.
active treatment (P<0.05). In a third study there
2. Bousquet J, Demoly P, Michael FB. Specific
was a loss of late asthmatic response to D.
immunotherapy in rhinitis and asthma. Annals of
pteronyssinus after 1 year which was maintained
Allergy, Asthma, &Immunology. 2001;87(Suppl
in the group that continued treatment.
1):38-42.

In the most recent update of the Cochrane
3. Yang X. Does allergen immunotherapy alter the
review (August 2003) Abramson MJ, Puy RM,
natural course of allergic disorders? Drugs.
and Weiner JM concluded allergy vaccine
2001;61(3):365-74.
immunotherapy can significantly reduce asthma
4. Moller C, Dreborg S, Ferdousi HA, Halken S,
symptoms and the requirement for asthma
Jacobsen L, et al. Pollen rhino conjunctivitis (The
medications. Both specific and nonspecific
PAT Study). J Allergy Clin Immunol 2002; 109:
251-6.
bronchial hyper-responsiveness decrease, but
5. Mastruzzo C, Crimi N, Li Gotti F, Sarva M,
improvement as measured by lung function tests
Mangano G, Paolino G, et al. Effect of specific
was inconsistent.
immunotherapy on clinical and inflammatory
Immunotherapy is the only currently
markers in patients with seasonal allergic rhinitis.
available immunologic treatment that controls and
J Allergry Clin Immunol 2002; 109: S91.
prevents allergic illness. Recent studies indicate
6. Gruber W, Eber E, Mileder P, Modl M, Weinhandl
immunotherapy is effective, its risk can be
E, Zach MS. Effect of specific immunotherapy
minimized and it is cost-efficient.10,11,12,13 In an era
with house dust mite extract on the bronchial
of expensive poly drug therapy, some degree of
responsiveness of Paediatric asthma patients.

untoward reactions and little proof of long-term
Clinical & Experimental Allergy 1999;29(2):176-
81.
impact, immunotherapy can be beneficial in
7. Creticos PS. The consideration of immunotherapy
asthmatic patients and have a long lasting effect.14
in the treatment of allergic asthma. Ann Allergy
It is the only treatment that can potentially modify
Asthma Immunol 2001;87:13-27.
the natural history of asthma. Upper airway
8. Ross RN, Nelson HS, and Feingold I.

disease is now recognized as critical in asthma
Effectiveness of specific immunotherapy in the
care, and IT treats both upper and lower airway
treatment of asthma: a meta-analysis of
disease simultaneously. Immunotherapy should be
prospective, randomized, double-blind, placebo-
considered very early when planning asthma
controlled studies. Clin Ther 2000;22: 329-341.
treatment because of the preventative and
9. Sigman K, Mazer B. Immunotherapy for
potentially long-lasting clinical and
childhood asthma: is there a rationale for its use?
Annals of Allergy, Asthma & Immunology 1996;
immunological improvement.15
76(4): 299-305.

Improvements in immunotherapy in the later
10. Malling MJ, Minimizing the risks of allergen-
portion of the twentieth century have been
specific injection immunotherapy. Drug Safety
dramatic and occurred because of enhanced
2000; 23(4): 323-32.
understanding of immunotherapy’s mechanism of
11. Gonzalez de la Cuesta C, Feijoo R, Rico P. A
action, proper selection of patients, recognition of
prospective safety-monitoring study of
the dose effect, and improved quality, consistency
immunotherapy in mite-allergy patients with mass-
and standardization of allergen vaccines.16 The
Can J Clin Pharmacol Vol 12 (2) Summer 2005:e198-e200; Jun. 17, 2005
e199
© 2005 Canadian Society for Clinical Pharmacology. All rights reserved.

---

Allergy vaccine immunotherapy in managing asthma
units-standardized extract. Allergy 1997; 52(5):
580-3.
12. Lockey RF, Nocoara-Kasti GL, Theodoropoulos
DS, Bukantz SC. Systemic reactions and fatalities
associated with allergen immunotherapy. Annals
of Allergy, Asthma & Immunology 2001;
87(Suppl): 47-55.
13. Mellerup MT, Hahn GW, Poulsen LK, Malling H.
Safety of allergen-specific immunotherapy.
Relation between dosage regimen, allergen extract,
disease and systemic side-effects during induction
treatment. Clinical & Experimental Allergy. 2000;
30(10):1423-9.
14. Cools M, Van Bever HP, Weyler JJ, Stevens WJ.
Long-term effects of specific immunotherapy,
administered during childhood, in asthmatic
patients allergic to either house-dust mite or to
both house-dust mite and grass pollen. Allergy
2000;55(1):69-73
15. Jacobsen L. Preventive aspects of immunotherapy:
prevention for children at risk of developing
asthma. Annals of Allergy, Asthma &
Immunology 2001; 87(Suppl 1): 43-6.
16. Li JT, Lockey RF, Bernstein IL, Portnoy JM and
Nicklas RA. Allergen immunotherapy: a practice
parameter. Ann Allergy Asthma Immunol 2003;
90:1-40.
17. Finegold I. Immunotherapy and Asthma. Journal
of Asthma 2003; 40Suppl: 31-5.
18. Finegold I. Analyzing meta-analyses of specific
immunotherapy in the treatment of asthma.


Annals of Allergy, Asthma & Immunology 2001;
87(Suppl 1): 33-7.




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Can J Clin Pharmacol Vol 12 (2) Summer 2005:e198-e200; Jun. 17, 2005
© 2005 Canadian Society for Clinical Pharmacology. All rights reserved.

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