1. health and fitness
2. disease
3. asthma

Walmart
Continuing Education
Managing Consequences of
the Allergic Response:
Focus on Asthma as
a Model of Atopic Disease
Expiry Date: April 8, 2012
Author: Tom Smiley, BSc. Pharm., PharmD.
CCCEP File # 899-0309
The Canadian Council on Continuing Education in Pharmacy
has approved this program for 1.75 CEUs.
Update for Pharmacists
Update for Pharmacists
Table of Contents
MANAGING CONSEQUENCES OF THE ALLERGIC RESPONSE:
Dear
Manitoba Pharmacists:
FOCUS
ON
ASTHMA
AS A
MODEL
OF
ATOPIC DISEASE . . . . . . . . 4
How is Asthma Control Defined? . . . . . . . . . . . . . . . . . . . . . . 9
Peak Expiratory Flow Meters for
Patients feel that pharmacists are the most trusted health
care
professionals.
Monitoring
of Asthma
Control . . . .With
. . . . . this
................9
Case . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
responsibility comes our duty to maintain and grow our knowledge base so that we are
able
to provide
exceptional
our patients.
Characterizing
the Epidemiology
and pharmaceutical care to Spirometry
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Etiology of Atopic Conditions . . . . . . . . . . . . . . . . . . . . . . . . . 4
At Wal-Mart Pharmacy, our valued LivingSmart Pharmacists
quarterly
continuing
Treatment ofreceive
Asthma Based
on Level
of Control. . . . . . . . . . . . 10
The
Pathophysiology
of
Allergic
Reactions
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
4
education modules on up to date topics on a regular basis. It is a pleasure for us to
Fast-acting
Bronchodilator
on Demand
. . . . . . . . . . . . . . . . . 10
share
some of these CEU modules with you. We hope
you are
able to utilize
this .wealth
Atopic vs. Non-atopic Asthma . . . . . . . . . . . . . . . . . . . . . . . . . 5
of knowledge to improve your patient’s health outcomes, and together, we will be able
Controller Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
to
grow
our profession
to new
heights.
Asthma
Symptoms
as a Consequence
of Allergic
Triggers . . . . 6
Best
Regards,
Triggers
of Allergic Responses – Asthma, Allergic Rhinitis . . . . 6
Focus on Leukotriene Receptor Antagonists . . . . . . . . . . . . . . 11
Laurie
Kaminsky,
B.Sc.Pharm
Immunotherapy
for Prevention
of
Professional
Services
Allergy-Mediated SymptomsManager
. . . . . . . . . . –. . Western
. . . . . . . . . Canada
......7
Wal-Mart Canada Corp.
Asthma Action Plans and Resources . . . . . . . . . . . . . . . . . . . . 11
How does immunotherapy work? . . . . . . . . . . . . . . . . . . . . . . . 7
Vijay Akileswaran, B.Sc.Pharm
Use of Allergen Extract
Immunotherapy
Professional
Services
Manager in– Eastern Canada
Specific
Allergic
Conditions
...........................8
Wal-Mart Canada Corp.
Risks Associated
Louise
Hostewith Allergen Immunotherapy . . . . . . . . . . . . 8
Director, Professional Services
Omalizumab: A Biological Response Modifier for
Wal-Mart
Canada Corp.
Treatment of Allergic Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Anaphylaxis – An Overview . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Pharmacologic Management of Acute Anaphylaxis . . . . . . . . . 12
Precautions for People at Risk for Anaphylaxis . . . . . . . . . . . . 13
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
QUIZ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Current Levels of Asthma Management –
Challenges and Opportunities . . . . . . . . . . . . . . . . . . . . . . . . . 9
Accreditation requirements:
A mark of 70% or greater is required on the quiz questions to earn the accredited number of CEUs. A
participant who fails a post-test may have one opportunity to re-do the test without being advised which
questions were incorrect the first time. Following the second attempt, whether a pass or fail, the correct
answers and rationale will be provided to the participant.
Disclosure Statement:
The Author and Expert Reviewers declare no real or perceived conflict with the sponsor company.
Learning Objectives
After successful completion of this continuing education lesson pharmacists will be better able to:
• Discuss the epidemiology, etiology and pathophysiology associated with atopic conditions
• Describe different allergy/asthma triggers and methods for avoidance
• Recommend immunization strategies and omalizumab therapy for attenuation of allergy and asthma
symptoms in patients meeting appropriate criteria
• Aid patients in assessment of asthma control and understanding of asthma severity
• Recommend appropriate stepwise therapy for asthma
• Recommend appropriate treatment of anaphylaxis
2
2
Managing Consequences of the Allergic Response: Focus on Asthma as a Model of Atopic Disease
Managing Consequences of the Allergic Response: Focus on Asthma as a Model of Atopic Disease
Update for Pharmacists
Update for Pharmacists
Table of Contents
MANAGING CONSEQUENCES OF THE ALLERGIC RESPONSE:
FOCUS ON ASTHMA AS A MODEL OF ATOPIC DISEASE . . . . . . . . 4
Case . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Characterizing the Epidemiology and
Etiology of Atopic Conditions . . . . . . . . . . . . . . . . . . . . . . . . . 4
The Pathophysiology of Allergic Reactions . . . . . . . . . . . . . . . 4
Atopic vs. Non-atopic Asthma . . . . . . . . . . . . . . . . . . . . . . . . . 5
Asthma Symptoms as a Consequence of Allergic Triggers . . . . 6
Triggers of Allergic Responses – Asthma, Allergic Rhinitis . . . . 6
Immunotherapy for Prevention of
Allergy-Mediated Symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
How is Asthma Control Defined? . . . . . . . . . . . . . . . . . . . . . . 9
Peak Expiratory Flow Meters for
Monitoring of Asthma Control . . . . . . . . . . . . . . . . . . . . . . . . . 9
Spirometry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Treatment of Asthma Based on Level of Control. . . . . . . . . . . . 10
Fast-acting Bronchodilator on Demand . . . . . . . . . . . . . . . . . . 10
Controller Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Focus on Leukotriene Receptor Antagonists . . . . . . . . . . . . . . 11
Asthma Action Plans and Resources . . . . . . . . . . . . . . . . . . . . 11
Anaphylaxis – An Overview . . . . . . . . . . . . . . . . . . . . . . . . . . 12
How does immunotherapy work? . . . . . . . . . . . . . . . . . . . . . . . 7
Pharmacologic Management of Acute Anaphylaxis . . . . . . . . . 12
Use of Allergen Extract Immunotherapy in
Specific Allergic Conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Precautions for People at Risk for Anaphylaxis . . . . . . . . . . . . 13
Risks Associated with Allergen Immunotherapy . . . . . . . . . . . . 8
Omalizumab: A Biological Response Modifier for
Treatment of Allergic Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
QUIZ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Current Levels of Asthma Management –
Challenges and Opportunities . . . . . . . . . . . . . . . . . . . . . . . . . 9
Accreditation requirements:
A mark of 70% or greater is required on the quiz questions to earn the accredited number of CEUs. A
participant who fails a post-test may have one opportunity to re-do the test without being advised which
questions were incorrect the first time. Following the second attempt, whether a pass or fail, the correct
answers and rationale will be provided to the participant.
Disclosure Statement:
The Author and Expert Reviewers declare no real or perceived conflict with the sponsor company.
Learning Objectives
After successful completion of this continuing education lesson pharmacists will be better able to:
• Discuss the epidemiology, etiology and pathophysiology associated with atopic conditions
• Describe different allergy/asthma triggers and methods for avoidance
• Recommend immunization strategies and omalizumab therapy for attenuation of allergy and asthma
symptoms in patients meeting appropriate criteria
• Aid patients in assessment of asthma control and understanding of asthma severity
• Recommend appropriate stepwise therapy for asthma
• Recommend appropriate treatment of anaphylaxis
2
Managing Consequences of the Allergic Response: Focus on Asthma as a Model of Atopic Disease
Managing Consequences of the Allergic Response: Focus on Asthma as a Model of Atopic Disease
3
Update for Pharmacists
Update for Pharmacists
MANAGING CONSEQUENCES OF THE ALLERGIC RESPONSE:
FOCUS ON ASTHMA AS A MODEL OF ATOPIC DISEASE
Case
Julie is a 25 year old lady who is pregnant with her first
child. Julie has seasonal allergies as well as allergies to
dust and moulds. She also has asthma. Julie’s husband
gets hayfever in the fall of the year but does not have
asthma. Julie wants to do whatever she can to reduce her
child’s risk for allergies. She is wondering if her child will
have allergies no matter what she does.
Characterizing the Epidemiology and
Etiology of Atopic Conditions
The incidence of immunoglobulin E (IgE)-mediated medical
conditions such as asthma, allergic rhinitis, and atopic dermatitis
are rising in Canada and around the world.1, 2 It is interesting
to note, however, that the prevalence of these allergy-mediated
conditions varies widely across Canada and between different
countries. 2 This suggests that the causes of these conditions
are multifactorial, with atopy but one of many factors involved
in pathogenesis.3 Allergic conditions have been referred to as
“polygenic,” meaning that several genes on different chromosomes
are involved in causing these disorders. Although a family history
of allergic disease is a strong predisposing factor, the rapid
increase in prevalence of atopic conditions cannot be explained by
this factor alone.3
Many theories have been offered in an attempt to explain the
increase in prevalence of atopic conditions. These have been based
on the following epidemiologic observations:
• Increase in atopic conditions has occurred in industrialized
Western countries.
• Prevalence is higher in urban than in rural areas.
• Prevalence is higher in privileged socioeconomic groups and
smaller families.
There is an increasing prevalence of asthma associated with
fast-paced industrialization in developing countries. Potential
consequences of the development of Western societies causing
increased risk for atopy may include increased exposure to
allergens and to both outdoor and indoor pollution as well as
changing lifestyle factors such as diet, body weight, antibiotic
use, and stress.2 One hypothesis suggests increased use of topical
corticosteroids may play a role, noting that the use of these
agents and the increase in prevalence of atopic diseases were
coincidental.4 In summary, it is apparent that for expression of
atopic disorder to occur, a complex interaction of genes with
environmental factors is required.3
Case (continued)
Julie is wondering if there is anything specific she can do
to reduce her child’s chance of getting asthma and/or
allergies. Will breastfeeding help? Should they get rid of
their dog? Is there any preventive medication that can be
given?
Clinical Practice Pearl:
Parents who are themselves atopic may be concerned about
the possibility of their child inheriting the condition.
The Canadian Pediatric Asthma Consensus Guidelines
have recommended actions that may protect against
development of allergy and asthma:5
• Do not expose fetus or infant to environmental tobacco
smoke. Passive exposure to tobacco smoke is one of the
strongest domestic and environmental risk factors for
developing recurrent coughing/wheezing or asthma
symptoms at any age during childhood.6
• The guidelines suggest that “Promotion of exclusive
breastfeeding for at least four months seems reasonable.”
However, recent evidence suggests that while exclusive
breastfeeding seems to reduce risk for wheezing episodes
in children less than four years of age (often associated
with respiratory infections), the effect on risk of
developing asthma in the long-term is not clear.7
For families where both parents are atopic, there is
maternal asthma, or both parents have asthma, the
guidelines recommend against the presence of a cat or dog
in the house. However, a recent meta-analysis suggests
that while dogs may increase asthma risk in an atopic
individual, cat exposure may actually be protective.8 More
studies with exact measurement of exposure are required
to clarify this issue.
The Pathophysiology of Allergic Reactions
The onset of increased IgE levels and eosinophilia is preceded by a
series of events as follows:9
Antigen is taken up by mucosal dendritic cells (often
Langerhans’ cells in the airways) and presented to T lymphocytes
(often in a draining lymph node).
• T lymphocytes are of the T helper 1 (Th1) or T helper 2
(Th2) type. T lymphocytes with the Th2 cytokine profile
increase synthesis of interleukin 4 (IL-4) and interleukin
13 (IL-13) which in turn promote IgE synthesis by B
lymphocytes.(see Figure 1). In phase 1, IgE fixates to mast
cells and basophils (see Figure 1)9 Pathways favouring the
Th1 cytokine profile inhibit B lymphocyte production of
IgE (see Figure 1).
• When the person with allergy is re-exposed to the allergen
the second and third phases occur. Cross-linking of
IgE bound to mast cells trigger the release of vasoactive
mediators (e.g., histamine, leukotrienes, prostaglandin
D2 and kinins) from the mast cells (see Figure 1). For an
overview of the effects of some of these mediators on allergic
rhinitis and asthma please refer to Table 1.
• IgE-induced mast cell degranulation is followed by a third
or late-phase reaction, a second wave of hypersensitivity
responses occurring many hours after the acute reaction, and
dependent upon increased eosinophil levels. This phase is
associated with hyper-responsiveness to inhaled irritants and
allergens.10
Consequences of the Allergic
Response:
Focus on Asthma
a Model
of Atopic
Disease
3
4Managing
Managing
Consequences
of the as
Allergic
Response:
Focus
on Asthma as a Model of Atopic Disease
Update for Pharmacists
Update for Pharmacists
Figure 1: The Pathophysiology of Allergic Responses (Adapted from Ref. 5)
Allergens
Dendritic
Cell
(airway)
Dendritic
Cell
(lymph node)
Interferon γ
Inhibits B lymphocyte
production of IgE
Th1
B lymphocytes
Th0
IgE
Synthesis
IL4, IL 13
Promotes B lymphocyte
production of IgE
Th2
Allergens
Prostaglandin D2
Mast
Cell
Leukotrienes
Table 1: Mediators of Signs and Symptoms of Asthma and
Allergic Rhinitis9
Mediator
Histamine
Leukotrienes
Signs and
Symptoms
Allergic Rhinitis
Itch
Sneeze
Rhinorrhea
Obstruction
Possible
rhinorrhea
Obstruction
Kinins
Obstruction
Prostaglandins
Obstruction
Endothelin
Itch
Sneeze
Rhinorrhea
Asthma
Bronchoconstriction
Plasma protein
exudation
Mucus secretion
Bronchoconstriction
Plasma protein
exudation
Mucus secretion
Bronchoconstriction
Cough
Bronchoconstriction
(PG E2, PG D2)
Antibronchoconstrictor
(PG E2)
Cough (PG E2)
Bronchoconstriction
Kinin
Histamine
Atopic vs. Non-atopic Asthma
The strongest predisposing factor for the development of asthma
is atopy (hereditary allergy). A common first presentation of
asthma in a child would be associated with a positive family
history of asthma and allergy to tree and grass pollen, house dust
mites, household pets, and moulds.11
Case 1 (continued):
Julie’s child Jimmy is now 2 years old and Julie has heard
him wheezing this week. Jimmy also has a runny nose.
Julie wants to know if she should assume he has asthma.
The diagnosis of asthma in preschool children is difficult
because wheezing early in life can occur in more than half of
all children.12 Most wheezing episodes are associated with viral
respiratory illness. Therefore, it is very important that parents with
young children who have had a wheeze do not automatically jump
to the conclusion that their child has asthma. Approximately 60%
of children with infantile wheeze will be healthy at school age.6
Preschool wheezing can be divided into four categories:6
• Transient wheezing – Wheezing during the first 2-3 years of
life, but not after the age of three years.
• Nonatopic wheezing – Mainly triggered by viral infection
and tends to resolve later in childhood.
4
Managing
Consequences
of the Allergic
Response:
FocusDisease
on Asthma
as a Model of Atopic Disease
Managing
Consequences of the Allergic
Response:
Focus on Asthma
as a Model
of Atopic
5
Update for Pharmacists
• Persistent asthma – Wheezing associated with the following:
• Clinical manifestations of atopy (eczema, allergic rhinitis
and conjunctivitis, food allergy), blood eosinophilia, and/
or elevated total immunoglobulin E (IgE).
• Specific IgE-mediated sensitization to foods in infancy
and early childhood, and subsequently to common
inhaled allergens.
• Inhalant allergen sensitization prior to three years of age,
especially with sensitization and high levels of exposure to
specific perennial allergens in the home.
• A parental history of asthma.
• Severe intermittent wheezing – Infrequent acute wheezing
episodes associated with the following:
• Minimal morbidity outside of time of respiratory tract
illness.
• Atopic characteristics, including eczema, allergic
sensitization and peripheral blood eosinophilia.
Atopic asthma is likely to persist whereas non-atopic asthma is
most likely to resolve before adulthood. A clinical index for the
diagnosis of asthma has been used to help predict which children
will likely go on to have persistent asthma.5, 13
Stringent index: 3 or more episodes of wheeze during the
first 3 years of life with:
• parental history of at least one of the major risk factors:
i. asthma
ii. eczema
or
• 2 of 3 minor risk factors:
i. eosinophilia
ii. wheezing without colds
iii. allergic rhinitis
Loose index: any wheezing during the first 3 years of life plus:
• 1 major or 2 minor risk factors
Asthma Symptoms as a Consequence
of Allergic Triggers
Asthma affects approximately 8.4% of Canadians.14 The Adult
Asthma Consensus Guidelines Update 2003 supports the
following definition of asthma:15
• Characterized by paroxysmal or persistent symptoms such as
dyspnea, chest tightness, wheezing, sputum production, and
cough associated with variable airflow limitation and airway
hyper-responsiveness to endogenous or exogenous stimuli.
• Inflammation and its effects on airway structure are
considered to be the principle mechanisms promoting the
development and maintenance of asthma symptoms.
Clinical Practice Pearl:
Atopic dermatitis (eczema) is a common precursor to
the development of asthma. Parents of children with
atopic dermatitis should be educated about the signs and
symptoms of asthma.
Update for Pharmacists
Similar to other atopic conditions, the prevalence of asthma has
increased over the past number of years to epidemic proportions
in Canada and the rest of the industrialized world. It is the most
common chronic disease in children.12 Studies have shown that
atopic dermatitis is a common precursor to the development of
asthma.16
In atopic (i.e., allergic) asthma, the inhalation of specific
allergens produces immediate bronchoconstriction that improves
spontaneously over an hour or is easily reversed by a �-agonist.
A second bronchoconstriction response often occurs 4-12 hours
later (known as the late asthmatic response). This response is often
more severe, more prolonged, and more difficult to reverse with
bronchodilators. Corticosteroids can block the late asthmatic
response but bronchodilators do not.11
If long-term airway inflammation resulting in asthma is not
controlled, airway remodeling (thickening of the airway wall
basement membrane) may occur. This refers to changes in
structure of the amount and composition of the extracellular
matrix in the airway wall. This may result in airflow obstruction
becoming only partially reversible.11
Asthma and allergic rhinitis are no longer viewed as having
distinct causes.2 Both nose and lower airways respond to
stimulation by irritant substances. While increased blood flow
is the main contributor to exacerbations of nasal obstruction
in allergic rhinitis, smooth muscle constriction and airway
narrowing is the primary cause of symptoms in asthma. Although
eosinophilia is a characteristic feature of both diseases, in allergic
rhinitis the mucosal eosinophilic response is strongly related to the
antigenic load. In asthma, bronchial eosinophilia is prominent. In
both asthma and allergic rhinitis there is epithelial accumulation
of mast cells displaying allergen-induced activation, which results
in the production of pro-inflammatory mediators including
histamine, cytokines, prostaglandins, leukotrienes, tryptase, and
kinins. Each of these mediators cause symptoms in asthma and
allergic rhinitis (see Table 1). These pro-inflammatory mediators
are important targets for current and future therapies.
Triggers of Allergic Responses –
Asthma, Allergic Rhinitis
Studies have shown that early and persistent exposure aeroallergen
sensitization confers a higher risk for development of asthma and
allergic rhinitis compared to later development of sensitivity.17
Allergen exposure leads to sensitization and the triggering of
symptoms.1 Studies where a potential allergen is removed before
sensitization can occur have had conflicting results. The complete
removal of a potential aeroallergen can be difficult to achieve and
sustain, and this should be balanced with controlling symptoms
through pharmacotherapy.6
Strategies that have been recommended for avoidance of allergy
triggers are outlined in Table 2.
Consequences of the Allergic
Response:
Focus on Asthma
a Model
of Atopic
Disease
5
6Managing
Managing
Consequences
of the as
Allergic
Response:
Focus
on Asthma as a Model of Atopic Disease
Update for Pharmacists
Update for Pharmacists
Table 2: Allergens: Recommended Avoidance Strategies*
Allergen
Grass, tree, weed and
flower pollen
Dust mites (present in
house dust)
Moulds (may be present
in damp basements,
closets, bathrooms, and
upholstered furniture, and
other places)
House pets (animal dander
can stay in carpets and
furniture for 4 - 6 weeks
and remain in air for
months after the animal
leaves)
Drugs
Food allergens
Smoke from tobacco and
fires – environmental
factors can trigger allergies
(allergic rhinitis and
asthma)
Recommended Actions To Avoid Triggers
• Use an air conditioner and keep doors and windows shut as much as possible.
• Vacation in areas where pollen counts are low.
• Limit outdoor activities when pollen counts are high.
• Bathe or shower and change clothes after being outdoors during allergy season.
• Dry clothes in a vented dryer instead of outside, where pollen may collect.
• Use a cover for the bed mattress and box spring that is allergen- impermeable (does not allow
allergens through material).
• Use pillow cases that are allergen-impermeable and airtight.
• Wash bedding in hot water at least 55o C (130o F) at least once a week. Dry in a hot dryer.
• Clean surfaces with a damp cloth at least weekly.
• Don’t use carpets or select carpets with low pile.
• Choose vinyl, leather, or plain wooden furniture instead of fabric-upholstered furniture.
• Vacuum floors at least weekly with a vacuum cleaner with integral HEPA filter and double-thickness
bags.
• Limit clutter and knickknacks that collect dust. Keep dust-accumulating objects in closed cupboards.
• Keep relative humidity in home low (<50%); use a dehumidifier if necessary.
• Replace curtains with blinds or easily washable curtains.
• Remove stuffed toys from bedrooms or hot wash/freeze them.
• Use a cleaning solution that contains 5% bleach to clean the tub and shower area and any other places
where mould and mildew grow (should be done by a non-allergic individual).
• Keep humidity in home below 50% to reduce mould growth.
• Dry sheets and clothing in a vented dryer, as mould s may collect if hung outside to dry.
• Refrain from walking in uncut fields, working with compost or dry soil, and raking leaves.
• Removal of the pet from the home is the most effective approach. Where removal is not possible:
• Keep pets out of the main living areas and bedrooms.
• Brush pet outdoors to remove loose hair and allergens and wash pet at least once a week (to be done
by non-allergic individual).
• Keep the pet outside as much as possible.
• Install a high-efficiency particulate air cleaner (HEPA) in the home.
• When necessary, find a good home for the pet.
• Cats tend to cause more problems than dogs.
• Remove carpeting or vacuum frequently.
• Avoid drugs that have been identified as allergens (such as ASA, NSAIDS). Non-selective betablockers (e.g., propranolol) should not be used by people with asthma.
• Identify and avoid food allergens (most common: eggs, milk, peanuts, shellfish, fish, soy, and wheat).
• Keep home smoke-free.
• Avoid areas where smoking is allowed.
• Encourage family members and/or caregivers to quit smoking.
• Use airtight stove/fireplaces if wood must be burned.
• Do not burn leaves in autumn.
* Adapted from reference
Immunotherapy for Prevention of Allergymediated Symptoms
role of immunotherapy in allergic diseases varies according to the
atopic condition.
How Does Immunotherapy Work?
In order to understand the most recently accepted theory
of the mechanism of action of SIT, we need to build on the
pathophysiological process outlined in Figure 1. In addition to
Th1 and Th2 cells, a third type of T-cell referred to as regulatorysuppressor T-cells (TReg cells) has been identified.19 These
cells have immunosuppressive function and cytokine profiles
distinct from either Th1 or Th2 cells. They are able to inhibit the
development of allergic Th2 responses and play a major role in
allergen SIT. Recent evidence suggests that production of TReg
cells and suppressive cytokines IL-10 and TGF-� (transforminggrowth factor beta cells) are induced by SIT.19 These, in turn,
Prevention is always the best strategy for management of disease.
The immune reaction which is stimulated by allergy triggers as
described in Table 2, and results in symptoms of asthma and
allergic rhinitis can be attenuated by immunotherapy.
Specific immunotherapy or SIT (subcutaneous injection of
small amounts of allergen) inhibits the progress of IgE-mediated
allergic diseases such as asthma and allergic rhinitis.18 It is an
interesting approach to management of allergies that addresses
the cause of hypersensitivity to antigens at the cellular level. The
6
Managing
Consequences
of the Allergic
Response:
FocusDisease
on Asthma
as a Model of Atopic Disease
Managing
Consequences of the Allergic
Response:
Focus on Asthma
as a Model
of Atopic
7
Update for Pharmacists
Update for Pharmacists
suppress proliferative and cytokine responses against the major
allergens and their T-cell-recognition sites.19
associated benefits and risks, including the importance of adhering
to the immunotherapy schedule.12
Use of Allergen Extract Immunotherapy in
Specific Allergic Conditions
Risks Associated with Allergen
Immunotherapy
Case 1 (continued)
Jimmy is now four years old and has allergic rhinitis. Julie
has heard that allergen immunotherapy can help Jimmy
with his symptoms and potentially even prevent him from
getting asthma. Is that true?
Allergen immunotherapy is effective in the management
of allergic asthma, allergic rhinitis, and stinging insect
hypersensitivity.20 It may also prevent the development of
asthma in children with allergic rhinitis.20 Clinical study suggests
that SIT consisting of house dust mite preparation is able to
improve eczema in patients with atopic dermatitis and reduces
the need for topical corticosteroids. This indication for allergen
immunotherapy is still under investigation.18
Clinical indications for allergen immunotherapy include the
following:20
• In patients with allergic asthma:
• Symptoms of asthma after natural exposure to
aeroallergens, demonstrable evidence of clinically relevant
specific IgE antibodies, and one of the following:
• Poor response to pharmacotherapy or allergen
avoidance
• Unacceptable adverse effects of medication
• Desire to avoid long-term pharmacotherapy and
reduce the cost of medication
• Coexisting allergic rhinitis and allergic asthma
• In patients with allergic rhinitis:
• Symptoms of allergic rhinitis after natural exposure
to aeroallergens, demonstrable evidence of clinically
relevant specific IgE antibodies (i.e., skin-testing and/or
immunological assay) and one of the following:
• Poor response to pharmacotherapy or allergen
avoidance
• Unacceptable adverse effects of medications
• Desire to avoid long-term pharmacotherapy and
reduce the cost of medication
• Coexisting allergic rhinitis and asthma
• Possible prevention of asthma in children
• In patients with reactions to Hymenoptera (ants, bees,
wasps) stings:
• History of a systemic reaction to a Hymenoptera
sting (especially if the reaction was associated
with respiratory or cardiovascular symptoms) and
demonstrable evidence of clinically relevant specific
IgE antibodies
• Age > 16 years, history of a systemic reaction limited
to the skin, and demonstrable evidence of clinically
relevant specific IgE antibodies
• History of a systemic reaction to imported fire ant
and demonstrable evidence of clinically relevant
specific IgE antibodies
When speaking with patients about allergen immunotherapy
options, health professionals need to educate patients around the
In general, the risk of fatal and nonfatal systemic reactions after
administration of allergenic extract is very low. Circumstances
which may increase such risk include:20
• Unstable steroid-dependent asthma
• Any medical condition that would compromise a patient’s
ability to withstand a systemic anaphylactic reaction. This
would include uncontrolled hypertension (because use of
epinephrine to treat systemic symptoms could be dangerous),
unstable angina or recent myocardial infarction
• Patients who are unable to communicate. They may not be
able to report signs or symptoms of systemic reaction
• A high level of allergic reactivity based on diagnostic tests
(usually immediate hypersensitivity skin tests)
• A history of previous systemic reactions to allergen
immunotherapy
• Starting a new vial of extract
• Asthmatic symptoms present immediately before receiving
an injection of allergenic extract
• Concomitant treatment with �-adrenergic blocking agents
• Administration of pollen extracts
• Rate of increase in the dose of allergenic extract that is too
rapid considering the patient’s degree of hypersensitivity
Treatment of anaphylaxis resulting from administration of
allergenic extracts is essentially the same as the treatment of
anaphylaxis from other causes (epinephrine is the treatment of
choice). Most severe reactions develop within 20 to 30 minutes
after the immunotherapy injection, and rarely an anaphylactic
reaction may be delayed for longer than one hour. Therefore, most
health professionals administering immunotherapy will have their
patients wait one-half hour in the office after administration of the
injection.
Case (continued)
Julie has found her asthma worsening lately and has
had difficulty keeping her symptoms controlled. Her
environment hasn’t changed, she is compliant with her
prescribed therapy and the severity of her asthma is
moderate to severe. She has heard of a “biologic” that
can help people with asthma. She would like you to tell
her more about it.
Omalizumab: A Biological Response
Modifier for Treatment of Allergic Asthma
Omalizumab is a recombinant humanized monoclonal antibody
indicated for treatment of moderate to severe persistent asthma in
persons 12 years or older who have had a positive skin test or in
vitro reactivity to a perennial aeroallergen and whose symptoms
are inadequately controlled with inhaled corticosteroids. 21 It
improves asthma symptoms by binding to the IgE molecule and
inhibiting the binding of IgE to its receptor on mast cells and
basophils (see Figure 1), thereby preventing the release of the
allergy symptoms mediators such as histamine. 21
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Clinical Practice Pearl:
Patients who have moderate to severe asthma and
consistently have poor control despite adherence to
treatment principles have an opportunity to improve
quality of life through treatment with omalizumab.
Studies have consistently shown that omalizumab reduces
the incidence and frequency of clinically significant asthma
exacerbations and reduces inhaled corticosteroid requirements in
patients with moderate to severe allergic asthma.22 The drug has
also been shown to improve asthma symptoms and lung function
and to improve asthma-related quality of life in these patients.22
In patients with severe asthma, omalizumab has been shown to
significantly reduce the level of exacerbations and the level of
severe exacerbations resulting in hospitalization or emergency care
in patients deemed to be at high risk because of recent emergency
treatment or prior intubation.22
Use of omalizumab is associated with side effects that include
injection site reactions (45%), viral (24%) and upper respiratory
tract infections (19%), headache (15%), sinusitis (16%), and
pharyngitis (10%). The occurrence of adverse events resulting
in clinical intervention (e.g., discontinuation of omalizumab
treatment) in clinical studies was 0.1% or less.21
Current Levels of Asthma Management –
Challenges and Opportunities
It is very evident that a large care gap exists between current and
optimal levels of asthma care. A large gap also exists in patients’
perceptions of good asthma control. In a survey of 893 Canadian
patients with asthma (The Reality of Asthma in Canada or TRAC
survey), 53% had uncontrolled asthma as per criteria outlined
below and 47% had controlled asthma.23 Only 3% of patients
actually thought they had uncontrolled asthma and 45% believed
that making one or two emergency trips to the hospital was just a
normal part of having the condition.23 Only 11% of patients had
written action plans and only one-half used them regularly.24
Approximately 61% of physicians surveyed in the TRAC study
admitted not using current Canadian asthma guidelines most or
all of the time.24
These findings represent an opportunity for pharmacists and
all health professionals to educate patients around appropriate
management of asthma, assessment of control and development
of action plans. Pharmacists are ideally positioned to play a critical
role in the collaborative education of patients.
How is Asthma Control Defined?
The Adult Asthma Consensus Guidelines Update 2003 offer the
following as criteria for the control of asthma:15
• Daytime symptoms less than 4 days per week
• Night-time symptoms less than one night per week
• Normal physical activity
• Mild, infrequent exacerbations
• No absenteeism from school or work due to asthma
• Fewer than 4 doses per week of a fast-acting �2-agonist
(apart from one dose/day before exercise)
• Forced expiratory volume in one second or peak expiratory
flow at 90% of personal best or greater
Update for Pharmacists
• Diurnal variability (difference between highest and lowest
value) in peak expiratory flow (PEF) of less than 10-15%
during the day.
The checklist above can be used with patients to determine if
their asthma is controlled. If any of the criteria above do not apply,
then a patient’s asthma is not controlled.
Alternatively, a 30-second asthma test™ has been developed to
help patients quickly determine if their asthma is controlled.
Figure 2: The 30-Second Asthma Test25
❏ I use my blue inhaler (reliever medication) 4 or more
times a week (except one dose/day for exercise).
❏ I cough, wheeze or have a tight chest because of my
asthma (4 or more days per week).
❏ Coughing, wheezing or chest tightness wakes me at night
(1 or more times a week).
❏ I stop exercising because of my asthma (in the past 3
months).
❏ I miss work or school because of my asthma
(in the past 3 months).
If you answered yes to one or more of the questions above,
talk with your doctor or certified asthma educator about how
you can better manage your asthma.
Peak Expiratory Flow Meters for
Monitoring of Asthma Control
Peak flow monitors measure the peak expiratory flow rate. They
can be used to:26
• Help determine the severity of asthma
• Check response to treatment during an acute asthma episode
• Monitor progress in treatment of chronic asthma and
provide objective information for any possible adjustments
in therapy
• Detect worsening in lung function, thereby avoiding a
possible exacerbation in asthma with early intervention
Predicted “normal” peak flow is determined by height, age and
gender. However, asthma control is best followed by comparing
daily peak flow readings with “personal best” reading. The
personal best is the highest peak flow number a patient can achieve
over a 2-3 week period when asthma is under control.26 Peak flow
should be recorded twice daily for two to three weeks, using the
same peak flow meter. It is important to understand that personal
best values in children will change as they grow and as disease
status changes.
The following steps should be followed when using a peak flow
meter:
• The device must read zero or be at base level to begin
• Take reading standing up whenever possible
• Patient should inhale as deeply as possible
• Meter should be placed in mouth and lips closed around the
mouthpiece
• Patient must blow out as hard and as fast as possible
• Patient must not cough, spit or let tongue block the
mouthpiece
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• The process repeated two additional times with the highest
of the three readings documented
• Be sure to remind the patient to clean the meter as
recommended by the manufacturer
Peak flow readings are generally interpreted as follows:
• Peak Expiratory flow rate (PEFR) of 80-100% of personal
best reflects controlled asthma
• PEFR of 50-80% of personal best means caution and a
temporary increase in asthma medication is indicated
• PEFR below 50% of personal best means “danger”/ Follow
instructions of Asthma Care Plan
• Results of peak flow monitoring should be linked (along
with asthma symptoms) to an appropriate asthma action care
plan
Peak flow meters must be checked regularly for accuracy and
reproducibility of results. This can be accomplished by asking
patients to take their meter to clinic visits so that readings can be
compared with spirometry.27
• A patient who is less than 80% of personal best is not well
controlled. A patient who is less than 60% of personal best
is in the “danger zone” and should immediately attend an
emergency department of a hospital.
Clinical Practice Pearl:
Peak flow monitors are recommended particularly for
those people with asthma who are poor perceivers of
worsening asthma for which they have required hospital
emergency treatment. For others, monitoring symptoms
and use of rescue medication is the most important means
for evaluating asthma control.
Spirometry
Spirometry is performed with a spirometer in a clinical setting to
measure lung volumes. The following is some terminology used:28
• Vital capacity (VC) is the volume of air blown off after
maximal inspiration to full expiration.
• Forced Expiratory Volume (FEV) is associated with
exhalation into the spirometer as forcefully and completely
as possible after maximal inspiration. The total volume of air
blown is known as the Forced Vital Capacity (FVC).
• The total volume of air blown in the first second of this
activity (as measured by the spirometer) is known as the
Forced Expiratory Volume in the first second (FEV1). In
general, healthy people can exhale at least 75-80% of their
FVC (i.e., FEV1/FVC) ratio in one second.
Pulmonary disorders generally fall into two categories: those
that restrict the lungs and thorax and those that obstruct them. In
a general sense, obstructive disease limits airflow during expiration
while restrictive disease limits airflow during inspiration.
Spirometry is used to confirm a diagnosis of asthma. A 12%
(preferably 15%) or greater improvement in FEV1 from baseline
15 minutes after use of an inhaled short-acting �2-agonist, or
a 20% or greater improvement after 10-14 days of ingested
prednisone, when symptoms are stable, indicates a reversible
airflow obstruction scenario consistent with asthma.28
clinic where the apparatus is available. Portable peak flow meters
are much more convenient for airflow monitoring. Although
spirometry can help to confirm a diagnosis of asthma, its value
is far more important in relating the subjective patient reported
symptoms to an objective measure of lung function.
Treatment of Asthma Based on Level of
Control
Treatment of asthma is based upon an individual’s current
asthma control, escalated if needed to gain control, only
after addressing other reasons for poor control, and
reduced to the least amount required to maintain asthma
control.29
Attention should always be paid to environmental control
(i.e., identifying asthma triggers and avoiding/preventing
exposure). Assessment of asthma control, triggers,
compliance with treatment regimens, inhaler technique
and co-morbidities should take place on a regular basis.
Although the triggers of asthma are often atopic in nature,
evidence points to control of airway inflammation and
bronchoconstriction as the most effective approach to
treatment.
Fast-acting Bronchodilator on Demand:
All individuals with asthma should have access to a fast-acting
bronchodilator for use as needed to treat acute symptoms. Inhaled
fast-acting β2-agonists are the preferred class and route of reliever
medication. These include:
• Several short-acting β2-agonists: salbutamol, terbutaline,
and fenoterol;
• One long-acting β2-agonist; formoterol. Formoterol
should only be used as a reliever in individuals on regular
inhaled corticosteroid (ICS) therapy in adults and
children aged 12 years and over, preferably in the same
inhaler device (i.e., combination budesonide/formoterol
preparation).29
Controller Therapy:
• Regular controller therapy is indicated in children 6 years
and over and adults who have one or more indicators of
poor control.
• Pharmacologic therapy should be determined based upon
an individual’s current asthma control, escalated if needed
to gain control, only after addressing other reasons for
poor control, and reduced to the least amount required to
maintain asthma control.
• Prescribed controller therapy should take into account both
current control and future risk for severe exacerbations.29
For the 2010 Canadian Respiratory Guidelines update:
Recommendations for the management of asthma in children
(6 years and over) and adults, visit http://www.respiratoryguidlines.
ca/sites/all/files/cts_asthma_slim_jim_2010.pdf.
All alterations in medication therapy should be considered a
trial, and effectiveness should be re-evaluated after a reasonable
period of time. After optimal asthma control is achieved,
medications should be reduced to the minimum necessary to
maintain control.
Spirometry is also helpful for monitoring asthma status.
A detailed account of therapies used in the treatment of
However, this is often impractical given the need to attend a
asthma other than leukotriene receptor antagonists which directly
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target leukotriene mediation of asthma symptoms prompted by
immune response, is beyond the scope of this lesson. Please refer to
previous continuing education lessons on asthma management for
more information.
Focus on Leukotriene Receptor Antagonists
Leukotriene Receptor Antagonists (LTRAs) act by preventing the
binding of the cysteinyl leukotrienes (LTC4, LTD4, LTE4) to their
binding sites in the human airway. Leukotrienes are released from
cells such as mast cells and eosinophils and cause inflammation,
bronchoconstriction, mucous secretion, vascular permeability,
and eosinophil recruitment. Currently available LTRAs include
montelukast and zafirlukast.
• LTRAs are a less effective option for monotherapy in mild
asthma for those patients who cannot or will not use ICS.15
In a systematic review which compared the effects of LTRAs
and ICS, patients treated with LTRAs were 60% more likely
to suffer an asthma exacerbation that required a course of
oral prednisone than patients using ICS.30 Patients using ICS
also had better symptom control and lung function. LTRAs
should not be used as monotherapy for moderate to severe
asthma.
• LTRAs are also a less effective option than LABA for add-on
therapy to ICS when low-dose ICS alone does not control
asthma in adults.15
• Montelukast (10 mg for adults, 5 mg for 6-14 years of
age, and 4 mg for 2-5 years of age) is an alternative to
as-needed salbutamol for prevention of exercise-induced
bronchoconstriction in adult and pediatric patients 2 years
of age and older.
• LTRAs may be used as an additive therapy to ICS in an
attempt to reduce the dose of ICS while maintaining control
(especially in children).
• LTRAs must not be used instead of short-acting �2-agonists
for treatment of acute asthma attacks.
• Montelukast and zafirlukast are associated with adverse
effects which include infrequent episodes of headache,
nausea, diarrhea and abdominal pain.31 Rare cases of
Churg-Strauss syndrome (eosinophilic vasculitis) have
been reported after stopping or reducing doses of oral
corticosteroids while taking a LTRA.27 Churg-Strauss
syndrome is characterized by symptoms which can include
worsened asthma, fever, weight loss, maculopapular rash,
purpura, rhinitis, cough, shortness of breath, chest pain,
diarrhea, abdominal pain and prostatitis.
• Montelukast may be used in children 2 years of age and over,
while zafirlukast is not indicated for children under 12 years
of age.
• Montelukast has not been documented to interact with
other drugs that would require dose adjustment. Zafirlukast
inhibits action of the cytochrome P450 2C9 isoenzyme
system. This is the likely mechanism for a 35% increase in
prothrombin time observed in a warfarin/zafirlukast drug
interaction study.32 Therefore INR should be monitored
closely if this drug combination is used.
• Other drugs metabolized by the cytochrome P450 2C9
should be monitored closely with use of zafirlukast. These
include tolbutamide, phenytoin, and carbamazepine.
Erythromycin and theophylline may decrease plasma levels
of zafirlukast, while ASA (650 mg four times daily) may
result in increased plasma levels of the drug. Increased levels
Update for Pharmacists
of zafirlukast may increase risk for adverse effects which may
include headache, nausea, diarrhea, abdominal pain.
• In patients with stable alcoholic cirrhosis, the clearance of
zafirlukast is reduced by approximately 50-60.32 Zafirlukast
is not recommended for use by patients with hepatic
impairment of any kind. If liver dysfunction is suspected
at any time (e.g., right upper quadrant abdominal pain,
enlarged liver, nausea, fatigue, lethargy, pruritus, jaundice),
zafirlukast should be discontinued.32
Asthma Action Plans and Resources
The Canadian Thoracic Society Asthma Management
Continuum – 2010 Consensus Summary for children six years
of age and over, and adults states that “written action plans
are a key component of care for all patients with asthma.” The
written plans referred to are often called “asthma action plans.”15
They allow patients to understand when to alter medication
management (e.g., increase doses of medications and/or add oral
prednisone therapy) and when to seek emergency help according
to the severity of symptoms. The action plan should be created
by the doctor or asthma-care specialist responsible for the
patient’s asthma care. Since a minority of patients report utilizing
an asthma action plan, this is an excellent awareness-raising
opportunity for pharmacists.
• Examples of action plans based on symptoms only (i.e.,
do not require a patient to have a peak flow meter) can be
found on the Internet at the Asthma Society of Canada
website at http://www.asthma.ca/adults/control/pdf/
AsthmaActionPlan_ENG.pdf.
• If a patient has a peak flow meter, action plans found at the
Canadian Lung Association website at http://www.lung.
ca/_resources/asthma_action_plan.pdf
• The action plan found at Family Physician Airways Group
of Canada at http://www.fpagc.com/AsthmaActionPlan2004.
pdf is also available.
All action plans include the message to go to emergency if peak
expiratory flow rate is 60% of personal best or lower.
Clinical Practice Pearl:
The Lung Association offers management tips and a
number of asthma management tools including an asthma
diary which allows patients to record asthma symptoms,
medication use and peak flow readings in their publication
“The Asthma Handbook.” It can be found at http://www.
lung.ca/pdf/handbook_web.pdf
These tools can all be downloaded and serve as excellent
resources for pharmacists to educate patients about their
condition. Asthma patients without action plans should be
encouraged to take one of the templates with them to their
principle asthma care provider at their next appointment.
The following are recommendations from the Canadian
Asthma Consensus Report on elements of patient asthma
education. These elements could be ticked off as you complete
patient education as part of an asthma clinic and with your clients
on an individual basis.
❏ Rationale and methods for identifying and avoiding irritants
and relevant allergens.
❏ Education about airway inflammation and bronchospasm.
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❏ Description of the rationale, correct use and side effects of
preventive medications and bronchodilators.
❏ Discussion of potential concerns or barriers to medication
use.
❏ Demonstration and practice of inhaler/spacer technique and
monitoring using symptoms or PEF meters.
❏ Description of criteria for control and steps to take when
control deteriorates (i.e., a written Asthma Action Plan).
❏ Discussion of the action plan and an attempt to improve
the patient’s and family’s understanding and willingness to
implement the plan when it is needed.
❏ Demonstration of techniques for successful communication
with health care professionals.
❏ Emphasis on the need for regular follow-up.
❏ Discussion of intolerance to sulfites or ASA.
❏ Specific information on food allergy.
❏ Discussion, when relevant, of conditions such as pregnancy.
If asthma is not controlled, review the following:
❏ Inhaler technique
❏ Potential barriers to compliance
• Cost
• Side effects
• Concerns
• Forgetfulness
❏ Asthma trigger exposure
❏ Other drugs: e.g., NSAIDs, beta-blockers
❏ Other potentially aggravating diseases: e.g., gastroesophageal
reflux disease (GERD), rhinosinusitis
Anaphylaxis – An Overview
The difference between survival and death of a patient with
severe allergy with or without associated asthma may ultimately
depend on a health professional’s and patient’s ability to
immediately recognize and appropriately treat an anaphylactic
reaction. Even when initially there are mild symptoms, the
potential for progression to a severe and even irreversible outcome
must be recognized.33
Any substance has the potential to cause anaphylaxis.34 The
most common causes of IgE-mediated anaphylaxis are insect stings,
medications, latex, peanuts and tree nuts (e.g., walnuts, hazelnuts,
almonds, cashews, pecans, and pistachios), shellfish, fish, milk,
eggs and wheat. Common anaphylactoid reactions include those
associated with NSAID use, opiates, and radiocontrast agents.34
Anaphylaxis is a systemic, generalized reaction; therefore, a wide
variety of clinical signs and symptoms may be present, including:34
• Skin – flushing, erythema, pruritus, urticaria, angioedema,
maculopapular rash
• Gastrointestinal – nausea, vomiting, abdominal pain,
diarrhea
• Neurologic – dizziness, weakness, seizures, syncope
• Ocular – pruritus, conjunctival injection (dilated vessels
causing redness of the eye), lacrimation
• Upper airway – nasal congestion, sneezing, hoarseness,
stridor, oropharyngeal or laryngeal edema, cough,
obstruction
• Lower airway – dyspnea, bronchospasm, tachypnea,
accessory muscle use, cyanosis, respiratory arrest
• Cardiovascular – Tachycardia, hypotension, arrhythmias,
myocardial ischemia/infarction, cardiac arrest
Update for Pharmacists
Symptoms usually appear within minutes but can occasionally
occur as long as one hour after exposure to the offending antigen.
Signs and symptoms resolve within hours of treatment. However,
in 20% of cases a second phase of symptoms occurs. These
“second-phase” symptoms occur at a mean of ten hours after the
initial reaction but may occur up to 38 hours later. Approximately
one-third of these reactions are more severe, one-third are of
the same severity, and one-third are less severe than the initial
reaction.33
Clinical Practice Pearl:
Although many authors recommend administration
of corticosteroids to prevent or minimize the second
phase (demonstrated beneficial in trials), there have
been several documented cases of patients receiving
corticosteroid therapy who went on to experience severe
biphasic reactions. Therefore, patients must be prepared
for a second reaction with epinephrine-based treatment
regardless of corticosteroid administration.33
Pharmacologic Management of Acute
Anaphylaxis
Parenteral epinephrine given intramuscularly (IM) is the
cornerstone of management for acute anaphylaxis (see Table 4).34
Administration of epinephrine is also indicated in the treatment
of life-threatening asthma attacks.35 The strong vasoconstrictor
action of epinephrine acts quickly to counteract vasodilation
and resultant capillary permeability. Epinephrine relaxes the
bronchioles through its action on smooth muscle, thereby
relieving wheezing and dyspnea. It also relieves angioedema and
hives.35 Epinephrine injection is available commercially in an
auto-injector format (EpiPen®,EpiPen Jr.® and Twin-Ject®). The
following are some instructions for the appropriate use of this
product:35
• The patients or someone at the scene who is familiar
with the use of the EpiPen® or EpiPen Jr.® (e.g., a parent or
teacher) should use the product at first sign of a recognized
anaphylactic reaction. Emergency help should then be
summoned for follow-up care at the nearest hospital.
• Both the adult and “junior” version of the auto-injector
deliver a single dose of 0.3 mL; the adult version contains
epinephrine 1:1000 (delivering 0.3 mg) and the junior
version contains epinephrine 1:2000 (delivering 0.15 mg).35
Clinical Practice Pearl:
Parents need to be made aware that once their child
weighs 30 kg or more, they should switch to the 0.3 mg
dose of epinephrine. There is a common tendency to
prescribe
EpiPen Jr.® for anyone under 12 years of age.
• Patients should be informed that there will be some liquid
left in the auto-injector after the injection is given, as only
0.3 mL of the 2 mL contained in the injector is actually
administered.
• Patients must be careful to store the auto-injector at room
temperature (between 15oC and 30o C.) It must not be left
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in extreme temperatures such as in the car during a heat wave
or a cold snap.
• If the solution in the auto-injector has turned brown, is
discoloured, or contains a precipitate, it must not be used.
• It is recommended that two Epipen® auto-injectors or one
Twinject® be kept handy at all times, as a second dose may be
needed should a second-phase reaction occur. Epinephrine
should be injected only in the thigh as outlined in the
package insert.
Figure 3: Patient Instructions for Use of EpiPen and EpiPen
Jr35
How do I use the EpiPen and EpiPen Jr auto-injectors?
(See package inserts for illustrations):
1. Pull off the grey safety release.
2. Inject EpiPen or EpiPen Jr into your outer thigh, even
through clothing if necessary. Do not inject EpiPen or
EpiPen Jr into your hands, feet, or buttock. Swing and
push black tip firmly into outer thigh so it “clicks” AND
HOLD on thigh for several seconds.
3. Massage the injected area for 10 seconds.
4. Seek medical attention immediately.
5. If you are able, go to the emergency room immediately
after using EpiPen auto-injector. Even after you have
sought medical help, stay where you can call 911 or
within easy access of a hospital for the next 48 hours.
If bronchospasm is present, inhaled �2-agonists such as
salbutamol are useful. Corticosteroids (e.g., methylprednisolone
125 mg IV or prednisone 50 mg PO) have been found useful in
minimizing second-phase reactions. Patients who are hypotensive
should receive intravenous fluid support with crystalloid or
colloid, and severe cases may require vasopressor agents such as
dopamine or high-dilution epinephrine (1:10,000).
Precautions for People at Risk for
Anaphylaxis
Allergen avoidance is the most reliable method for preventing
anaphylaxis (see Table 2). Patients with documented allergies
should wear identification such as a MedicAlert ™ bracelet. With
MedicAlert™, in the event of an emergency, the caregiver is
alerted to the possible cause of the incident and a 24-hour hotline
provides callers with immediate access to the patient’s medical
record. Health professionals can order MedicAlert™ application
forms online at https://www.medicalert.ca/en/health/order.asp
or by phoning 800-668-1507 between the hours of 9am and
5pm EST. Patients can also apply directly online at https://www.
medicalert.ca/en/join/
An excellent organization to refer patients and parents of
children with allergies to is Anaphylaxis Canada, which can be
found online at http://www.anaphylaxis.org/index.asp . This
website addresses issues associated with living with anaphylaxis
and provides links to services that would commonly be required
for people at risk for anaphylactic reactions.
Table 4: Pharmacologic Management of Acute
Anaphylaxis Reaction34
Drug
Epinephrine 1:1000, IM
Diphenhydramine IV, IM,
or PO
Ranitidine IV or PO
Corticosteroids:
Methylprednisolone IV or
prednisone PO
Frequency of Administration
Immediately, then every 5-15 min. as
needed*
Once patient’s condition is stabilized with
epinephrine and fluids, then every 4-6
hrs prn
Once patient’s condition is stabilized with
epinephrine and fluids, then every 8 hrs
prn
Once patient’s condition is stabilized with
epinephrine and fluids, then every 6 hrs
prn
Dose (Adult)
0.3 - 0.5 mL
25 - 50 mg
Dose (Child)
0.01 mL/kg (up to 0.3
mL)
1.25 mg/kg
50 mg IV or 150 mg PO
1.25 mg/kg IV
or 2 mg/kg PO
methylprednisolone 125 mg
IV or prednisone 50 mg PO
1 mg/kg IV or
1 mg/kg PO
* Until resolution or signs of palpitation, tremor, uncomfortable apprehension and
anxiety occur.
12
Managing
Consequences
of the Allergic
Response:
FocusDisease
on Asthma
as a Model of Atopic Disease
Managing
Consequences of the Allergic
Response:
Focus on Asthma
as a Model
of Atopic
13
Update for Pharmacists
Update for Pharmacists
Summary
Pharmacists are an important source of education for the atopic
patient. Patients with a family history of allergy are at higher
risk for all atopic conditions. People who have children with
atopic dermatitis or allergic rhinitis should be vigilant for signs
of asthma in their child. Avoidance of potential allergens is the
cornerstone for management of conditions associated with atopy.
Immunotherapy is a strategy that is associated with great relief for
many patients.
Pharmacists should ensure that patients understand how to
assess their level of asthma control and the potential that exists for
better quality of life through optimal asthma management. The
continuum
care promoted by the Canadian Asthma Consensus
Update forofPharmacists
Guidelines 2003 update, coupled with a raised awareness of
asthma monitoring and effective pharmacist and allied health
professional communication and intervention is essential to
helping patients gain and maintain control of their asthma
symptoms. Education of patients that includes development of a
care plan and understanding of their disease state is an important
role for pharmacists.
Pharmacists are an important resource for patients at risk for
anyphylactic reactions. Ensuring patients understand how and
when to use emergency epinephrine products is a critical education
piece for pharmacists to convey.
REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
Eichenfield LF, Hanifin JM, Beck LA et al. Atopic dermatitis and asthma:
parallels in the evolution of treatment. Pediatrics 2003;111(3):608-616.
Habbick BF, Pizzichini MM, Taylor B, Rennie D, Senthilselvan A, Sears MR.
Prevalence of asthma, rhinitis and eczema among children in 2 Canadian
cities: the International Study of Asthma and Allergies in Childhood. CMAJ
1999;160(13):1824-1828.
Arshad SH. Primary prevention of asthma and allergy. J Allergy Clin Immunol
2005;116(1):3-14.
Pampura AN. Prevalence of atopic diseases and the use of topical corticosteroids.
Is there any connection? Med Hypotheses 2005;64(3):575-578.
Becker A, Berube D, Chad Z et al. Canadian Pediatric Asthma Consensus
guidelines, 2003 (updated to December 2004): introduction. CMAJ 2005;173(6
Suppl):S12-S14.
Bacharier LB, Boner A, Carlsen KH et al. Diagnosis and treatment of asthma in
childhood: a PRACTALL consensus report. Allergy 2008;63(1):5-34.
Greer FR, Sicherer SH, Burks AW. Effects of early nutritional interventions on
the development of atopic disease in infants and children: the role of maternal
dietary restriction, breastfeeding, timing of introduction of complementary
foods, and hydrolyzed formulas. Pediatrics 2008;121(1):183-191.
Takkouche B, Gonzalez-Barcala FJ, Etminan M, Fitzgerald M. Exposure to
furry pets and the risk of asthma and allergic rhinitis: a meta-analysis. Allergy
2008;63(7):857-864.
Howarth PH. ABC of allergies. Pathogenic mechanisms: a rational basis for
treatment. BMJ 1998;316(7133):758-761.
Oettgen HC, Geha RS. IgE in asthma and atopy: cellular and molecular
connections. J Clin Invest 1999;104(7):829-835.
Self TH. Asthma. Applied Therapeutics: The Clinical Use of Drugs , 23.1-23.43.
2005. Lippincott, Williams & Wilkins.
Becker A, Watson W, Ferguson A, Dimich-Ward H, Chan-Yeung M. The
Canadian asthma primary prevention study: outcomes at 2 years of age. J Allergy
Clin Immunol 2004;113(4):650-656.
Castro-Rodriguez JA, Holberg CJ, Wright AL, Martinez FD. A clinical index
to define risk of asthma in young children with recurrent wheezing. Am J Respir
Crit Care Med 2000;162(4 Pt 1):1403-1406.
Health Canada. Respiratory Disease in Canada. Canadian Cataloguing in
Publication Data 2005; ISBN 0-663-30968-5.
Lemiere C, Bai T, Balter M et al. Adult Asthma Consensus Guidelines Update
2003. Can Respir J 2004;11(Suppl A):9A-18A.
Bergmann RL, Edenharter G, Bergmann KE et al. Atopic dermatitis in
early infancy predicts allergic airway disease at 5 years. Clin Exp Allergy
1998;28(8):965-970.
Warner JO. A double-blinded, randomized, placebo-controlled trial of cetirizine
in preventing the onset of asthma in children with atopic dermatitis: 18 months’
treatment and 18 months’ posttreatment follow-up. J Allergy Clin Immunol
2001;108(6):929-937.
18. Werfel T, Breuer K, Rueff F et al. Usefulness of specific immunotherapy in
patients with atopic dermatitis and allergic sensitization to house dust mites: a
multi-centre, randomized, dose-response study. Allergy 2006;61(2):202-205.
19. Akdis M, Blaser K, Akdis CA. T regulatory cells in allergy: novel concepts in
the pathogenesis, prevention, and treatment of allergic diseases. J Allergy Clin
Immunol 2005;116(5):961-968.
20. Joint Council of Asthma Allergy and Immunology. Practice parameters for
allergen immunotherapy. Ann Allergy 90, S1-S540. 2006.
21. Xolair Product Monograph. Compendium of Pharmaceuticals and Specialties .
2009.
22. Bousquet J, Cabrera P, Berkman N et al. The effect of treatment with
omalizumab, an anti-IgE antibody, on asthma exacerbations and emergency
medical visits in patients with severe persistent asthma. Allergy 2005;60(3):302308.
23. McIvor RA, Boulet LP, FitzGerald JM, Zimmerman S, Chapman KR. Asthma
control in Canada: no improvement since we last looked in 1999. Can Fam
Physician 2007;53(4):673-7, 672.
24. FitzGerald JM, Boulet LP, McIvor RA, Zimmerman S, Chapman KR. Asthma
control in Canada remains suboptimal: the Reality of Asthma Control (TRAC)
study. Can Respir J 2006;13(5):253-259.
25. The Lung Association. Asthma Management: The Asthma Handbook. http://
www.lung.ca/pdf/handbook_web.pdf . 2009. Accessed Mar. 17, 2009
26. American Academy of Asthma AaI. Tips to remember: What is a Peak Flow
Meter? http://www.aaaai.org/patients/publicedmat/tips/whatispeakflowmeter.stm .
2009. Accessed March 15, 2009
27. Boulet LP, Becker A, Berube D, Beveridge R, Ernst P. Canadian Asthma
Consensus Report, 1999. Canadian Asthma Consensus Group. CMAJ
1999;161(11 Suppl):S1-61.
28. Barreiro TJ, Perillo I. An approach to interpreting spirometry. Am Fam Physician
2004;69(5):1107-1114.
29. Lougheed MD, Lemiere C, Dell SD, et al. Canadian Thoracic Society Asthma
Management Continuum – 2010 Consensus Summary for children six years of
age and over, and adults. Can Respir J 2010;17:15-24.
30. Ducharme FM. Inhaled glucocorticoids versus leukotriene receptor antagonists
as single agent asthma treatment: systematic review of current evidence. BMJ
2003;326(7390):621.
31. McCormack D. Adult Asthma. Therapeutic Choices , 626-639. 2007. Canadian
Pharmacists Association.
32. Astra Zeneca. Accolate product monograph. 2009.
33. The diagnosis and management of anaphylaxis: an updated practice parameter.
J Allergy Clin Immunol 2005;115(3 Suppl 2):S483-S523.
34. Ellis AK, Day JH. Diagnosis and management of anaphylaxis. CMAJ
2003;169(4):307-311.
35. Epipen product monograph. Compendium of Pharmaceuticals and Specialties.
2009.
Managing
Consequences of the Allergic
Response:
Focus on Asthma
a Model
of Atopic
Disease
13
14
Managing
Consequences
of the as
Allergic
Response:
Focus
on Asthma as a Model of Atopic Disease
Quiz
Dear Pharmacist:
Below and on the back cover are the questions for the Wal-Mart Continuing Education lesson Managing Consequences of the Allergic Response: Focus on
Asthma as a Model of Atopic Disease. Please complete the answer card on the back cover by circling the correct answer to each question and drop the completed
card in the mail, or fax it to: The Manitoba Society of Pharmacists at 1-204-956-6686. The answer card can also be submitted online at www.msp.mb.ca.
Please
keep a photocopy for your records. You will be notified of your results within four to six weeks of receipt of your answer card.
QUIZ
1.
Which of the following statements about the epidemiology and
etiology of atopic conditions is true?
a. Family history of allergy-related disease is the sole
determinant of a child’s risk for IgE-mediated disease.
b. The incidence of IgE-mediated medical conditions is more
prevalent in underprivileged areas.
c. Prevalence of IgE-mediated disease is higher in urban than in
rural areas.
d. Outdoor pollution, but not indoor pollution plays a role in
prevalence of IgE-mediated disease.
5.
A patient tells you that his asthma is in good control. When you
ask, he says he has only been to emergency once this year because
of his asthma. Which of the following statements about asthma
control and perception of asthma control is true according to
The Reality of Asthma in Canada (TRAC) survey?
a. About 80% of survey participants had their asthma under
control.
b. Almost one-half patients surveyed thought that one to two
trips to emergency is normal for patients with asthma.
c. Less than one-half patients surveyed perceived their asthma
was under control.
d. Answers a and b are correct.
The Manitoba Society of Pharmacists
202-90 Garry St.
Winnipeg, MB R3C 4H1
A young lady is considering immunotherapy to reduce future
allergy symptoms. Which of the following statements about
immunotherapy is FALSE?
a. All patients with asthma are candidates for immunotherapy.
b. Patients receiving immunotherapy against hymenoptera stings
should be older than 16 years of age.
c. People with uncontrolled hypertension should not receive
immunotherapy,
d. Risk for reactions to immunotherapy is greater when a new
vial of extract is opened.
_______________________________
4.
_______________________________
A young mother comes to you and says she has noticed her child
wheezing on and off, especially when she has a cold, during her
first three years. Which of the following is your best response?
a. Don’t assume she has asthma. Many children have transient
wheezing during the first few years.
b. Wheezing is not common until after three years old in most
children. She will likely be diagnosed with asthma.
c. She will only get asthma if she first has allergic rhinitis.
d. Mother should take her daughter to the doctor for allergy
tests and possible immunotherapy.
From___________________________
3.
Place
Postage
Here
2. Which of the following allergy symptom mediators promote
bronchoconstriction?
a. kinins
b. leukotrienes
c. endothelin
d. all of the above
Answer Card
This is the answer card for the 2010 Wal-Mart Continuing Education lesson
Managing Consequences of the Allergic Response: Focus on Asthma as a Model
of Atopic Disease. Please circle the correct response to each question (there is
only one correct answer for each question), complete the information at the
bottom of the card and drop the completed card in the mail, or fax it to:
The Manitoba Society of Pharmacists at 1-204-956-6686. The answer card
can also be completed and submitted online at www.msp.mb.ca. Please keep a
photocopy of your completed Answer Card for your records. Thank you.
Quiz Answers
1.
2.
3.
4.
5.
6.
8.
9.
10.
a
b
c
d
a
b
c
d
a
b
c
d
a
b
c
d
a
b
c
d
a
b
c
d
a
b
c
d
a
b
c
d
a
b
c
d
6.
A gentleman tells you that his doctor has told him he he now
needs a long-acting β2-agonist addition to the short-acting
β2-agonist and inhaled corticosteroid (ICS) controller he is
currently using. Why would the doctor have prescribed the
additional treatment for him?
a. His Peak Expiratory Flow diurnal variation is 8%.
b. His peak flow meter reading was 91% of personal best.
c. He has daytime symptoms twice per week on average.
d. He has been using his short-acting β2-agonist once daily on
average for the last month.
7.
A doctor asks you what dose of omalizumab he should order for
an adult patient. Which of the following is your most appropriate
response?
a. Dose should be started at 150 mg SC every 4 weeks and
titrated upwards as needed.
b. Dose in adults should be 375 mg every 2 weeks.
c. Dose should be based on symptoms.
d. Dose should be based on serum IgE concentration and body
weight.
8. A physician would like your opinion on whether to use
montelukast or zafirlukast as add-on therapy for an atopic
individual who has severe asthma. Which of the following
statements about these two agents is true?
a. Zafirlukast is not metabolized by the Cytochrome P450 system
while montelukast is.
b. Zafirlukast but not montelukast is associated with increased
risk for Churg-Strauss syndrome.
c. Montelukast is indicated for children while zafirlukast is
indicated for only those older than 12 years.
d. Answers b and c are correct
9.
A patient tells you that he has heard a second phase reaction after
an initial anaphylactic reaction may occur. He wants to know
how long after the first reaction the second may occur.
a. Approximately 1-2 hours later
b. Up to 5 hours later
c. 10 hours to 38 hours later
d. Up to 3 days later
10. A patient wants to know more about the epipen® auto-injector.
Which of the following statements is FALSE?
a. If liquid is brown-coloured, auto-injector should be discarded.
b. It is recommended to leave auto injector in the car so it is
readily available on trips.
c. Two auto injectors or one TwinJect should be available at all
times.
d. Epinephrine should only be injected in the thigh.
Pharmacist Information
Name:_ ________________________________________________________
Membership Number:_ ____________________________________________
Address:________________________________________________________
______________________________________________________________
Tel:__________________________________ Fax:______________________
License Number:_ ________________________________________________
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