Transcript Asthma and Allergic Rhinitis: Acute and Chronic Management

Allergic Asthma:
Diagnosis and Treatment
Eddie W. Shields, MD
Arkansas Allergy and Asthma
Objectives
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Understand the relationship between asthma
and allergic rhinitis
Understand the pathophysiology of allergic
asthma
Learn the role of environmental control,
pharmacologic therapy, and allergen
immunotherapy in allergic asthma
Rhinitis and Asthma
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High prevalence, high cost illnesses
Both illnesses have a major effect of the sufferer’s
quality of life
Both illnesses have a strong association with allergy
Both rhinitis and asthma have common
inflammatory pathways
Improved control of rhinitis leads to improve
asthma outcomes
Leading Chronic Conditions*
in Children Aged <18 Years
80
70
60
Cases
per
1000
Children
N=3355
50
40
30
20
10
0
Hay Fever Asthma
Other
Skin Digestive Cardiac
Other
Respiratory Allergies Allergies Conditions Nonallergic
Conditions
Allergies
*Patient assessment.
Adapted from Newacheck et al. J Pediatr. 1994;124:40.
Allergic Rhinitis
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CHRONIC Inflammatory Disease of the Upper
Airways
35 million Americans have allergic rhinitis–
Prevalence of 10-20% of the population
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Productivity
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Peak prevalence in children and young adults
50% of patients have symptoms >4 months per year and
20% >9 months per year
28 million days of restricted activity
2 million lost school days
Cost of treatment
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$3.5 billion total cost associated with allergic rhinitis
treatment
Asthma
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CHRONIC Inflammatory Disease of the Lower
Airways
Affects about 3-4% of the populations; 7% of
children
Most common non-traumatic admission to
children’s hospitals in the U.S.
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Greater 200,000 hospitalizations per year in U.S.
Evidence of Causal Role of Allergies
in Asthma in Children
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Sensitization to indoor allergens and outdoor
fungi increases the risk for asthma
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The larger the size of the skin test reaction to house
dust mite, the more sensitive the patient is to
methacholine, a measure of bronchial hyperreactivity.
JK Peat, et al. N.Z. Med J 1994;24:270
Evidence of Causal Role of Allergies
in Asthma in Children
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Severity of asthma is related to the level of
allergen exposure
18 episodes of sudden onset, respiratory arrest in 11
patients, ages 11-25 years
 All occurred in summer and early fall
 10/11 skin test positive for Alternaria
 Peak Alternaria season is June to November
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O’Hollaren, et al. NEJM 1991; 324:359-63
Evidence of Causal Role of Allergies
in Asthma in Children
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Reduction of allergen exposure improves
asthma symptoms and pulmonary function and
reduces bronchial hyper-responsiveness.
Rhinitis in Asthmatic Children
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Approximately 80% of children presenting with
asthma have rhinitis (1)
Children with a history of allergic rhinitis are
more likely to suffer from exercise-induced
bronchospasm (2)
(1) Mercer et al. S Afr Med J 1991
(2) Bradsford et al. Int Arch Allergy Appl Immunol 1991
Allergic Rhinitis as a Risk Factor
for Developing Asthma, a 23 yr
Follow-up
Diagnosis Total at New
%
as
risk
asthma
freshman
AR
152
17
p value
10.5
<0.002
Non-AR
528
19
3.6
Total
690
36
5.2
Settipane et al. Allergy Proc 1994
Hypotheses for Links of Rhinitis
and Asthma
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Both associated with allergy
Common ciliated epithelium
Similar allergens are associated with both
conditions
Both have a familial link with atopy
Possible pathophysiological mechanism-sinobronchial reflex
Pathophysiology of
Allergic Rhinitis
and Asthma
Phase 1 – Sensitization
Antigenpresenting
cell
Allergen
Processed
allergen
B cell
CD4
T cell
Plasma cell
Adapted from Naclerio. N Engl J Med. 1991;325:860-869.
IgE antibodies
Intracellular
Pathogens
Interleukin 12
Interferon 
Interleukin 2
Cell-mediated
Immunity
TH1
TH0
Allergens
Interleukin 4
JAMA. 1997;278:1845.
TH2
Interleukin 2
Interleukin 5
Interleukin 13
Allergic Disease
Humoral Immunity
Phase 2 – Clinical Disease
Early
Phase
Late
Phase
Allergen
IgE antibodies
Mast
cell
Mediator
release
Blood
vessels
Nerves
Cellular
Infiltration
Late-phase
reaction
Eosinophils
Basophils
Monocytes
Lymphocytes
Hyperresponsiveness
Priming
Resolution
Complications
Irreversible
Disease?
Glands
Sneezing
Itching
Rhinorrhea
Congestion
Adapted from Naclerio. N Engl J Med. 1991;325:860-869
Overview of the Allergic Inflammatory
Cascade in Patients with IgE-mediated
Asthma
B lymphocyte
-switch
Allergic
mediators
Allergic
Inflammation:
eosinophils and
lymphocytes
Plasma cell
Release
of IgE
Allergens
Mast cells
Basophils
Allergic Exacerbation
IgE-dependent Release of Inflammatory
Mediators
Allergens
IgE
FcRI
Immediate Release
Granule contents:
Histamine, TNF-,
Proteases, Heparin
Sneezing
Nasal congestion
Itchy, runny nose
Watery eyes
Over Hours
Over Minutes
Lipid mediators:
Prostaglandins
Leukotrienes
Wheezing
Bronchoconstriction
Cytokine production:
Specifically IL-4, IL-13
Mucus production
Eosinophil recruitment
Management of Allergic Rhinitis
and Asthma
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Education
Environmental Control
Proper Pharmacologic Treatment
Allergen Vaccination (Immunotherapy)
Asthma Education
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Define asthma and explain treatment options
Need to adhere to treatment plan
Discuss patient’s fear about asthma and its treatment
Conduct regularly scheduled follow-up office visits
Provide written asthma action plan
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Treatment schedule, peak flow zones, and emergency
numbers
Environmental Control
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Major triggers of Allergic Rhinitis and Asthma
 Pollens
 Molds
 House dust mites
 Animals
 Insect aeroallergens (eg, moths)
ACAAI/AAAAI Joint Task Force. Ann Allergy Asthma Immunol.
1998;81:463.
Hackberry
Oak
Willow
Grass
Environmental Control Measures:
Pollen
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Close windows, doors
 Avoid window/attic fans
 A/C on recirculate
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Reduce outdoor exposure as practicality allows:
 When pollen counts are high
 Highest in early AM
 On sunny, windy days with low humidity
 Shower or bathe following exposure
ACAAI/AAAAI Joint Task Force. Ann Allergy Asthma Immunol. 1998;81:463518.
Mold
Environmental Control Measures:
Molds
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Remain in closed environment as practicality allows
 A/C units, though helpful, can harbor mold
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Avoid lawn mowing, raking leaves, etc
 Face masks can be of some value
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Avoid/remedy dampness
 Dehumidifier
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Minimize humidifier use
 If used, keep very clean
ACAAI/AAAAI Joint Task Force. Ann Allergy Asthma Immunol.
1998;81:463.
Environmental Control Measures:
House Dust Mites
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Vigorous methods necessary
 Ordinary vacuuming/dusting
have little effect
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Simple furnishings without
carpeting
 Especially bedroom, family
room, etc
 Plastic, leather, wood are
best
ACAAI/AAAAI Joint Task Force. Ann Allergy Asthma Immunol.
1998;81:463.
Environmental Control Measures:
House Dust Mites
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Wash bedclothes at 130oF
 Lower temperatures do not kill mites
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Allergen-proof pillows, mattresses, box springs
 Avoid/cover quilts and comforters
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Cleaning of duct work has no demonstrated value
in removing dust mites
ACAAI/AAAAI Joint Task Force. Ann Allergy Asthma Immunol.
1998;81:463.
Environmental Control Measures:
Animal Allergens
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All furry/feathered animals
Cat/dog reactivity found in 25% to 33% of patients
with AR
Avoidance most effective
 Remove pets from home, if possible
 Confine animal(s) to noncarpeted room (not bedroom)
 HEPA filter in animal room may reduce allergens
in rest of home
 Eliminate/move litter boxes
ACAAI/AAAAI Joint Task Force. Ann Allergy Asthma Immunol.
1998;81:463.
Environmental Control Measures:
Insect Allergens
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Debris of cockroaches, crickets, flies, moths, etc
Careful sanitation
 Eliminate open or standing food, dirty dishes
 Store garbage in tightly closed containers
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Roach traps
Consider professional extermination/relocation if
infestation is heavy
ACAAI/AAAAI Joint Task Force. Ann Allergy Asthma Immunol.
1998;81:463.
Environmental Control Measures:
Irritant Factors
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Avoid irritants
 Tobacco smoke
 Perfume, potpourri
 Formaldehyde
 School supplies/environment
 Markers
 Chalk dust
ACAAI/AAAAI Joint Task Force. Ann Allergy Asthma Immunol.
1998;81:463.
Medical Management of Asthma
Goals of Asthma
Management
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Primary goal
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The asthmatic patient should be to do ALL normal
activities
Other goals
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Maintain normal or near normal pulmonary function
Prevent chronic symptoms and recurrent exacerbations
No emergency department visits or hospitalizations
Prevent irreversible lung disease
Minimize need for rescue medications
Avoid adverse reactions from medications
Changes In Airway Morphology in
Asthma
Smooth muscle
contraction
Edema
Vasodilation
Infiltration of
inflammatory
cells
Loss of epithelium;
Thickening & fibrosis
of basement and sub-basement
membrane
Hypertrophy of
mucous gland,
hypersecretion
of mucus
Omalizumab Characteristics
 Humanized
 Binds
mAb against IgE
Murine CDRs*
(< 5% of molecule)
circulating IgE
regardless of specificity
 Forms
small, biologically inert
Omalizumab:IgE complexes
 Does
not activate complement
*CDR = complementarity-determining region
Adapted with permission from Boushey H. J Allergy Clin Immunol. 2001;108:S77-S83.
IgG1 kappa
Human
framework
(> 95% of molecule)
IgE Binds to Mast Cells at the
High Affinity Receptor (FcRI)
IgE molecule
FcRI binding site
FcRI receptor
IgE molecule
bound to mast cell
Mast cell
Omalizumab Blocks IgE
Binding to Mast Cells
IgE molecule
Omalizumab
Omalizumab
FcRI receptor
Mast cell
Allergen Immunotherapy
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The administration of low then sequentially
increasing doses of allergens in patients with
IgE mediated diseases:
 Allergic
Rhinoconjunctivitis
 Allergic Asthma
 Insect Sting Anaphylaxis
Immunotherapy
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Allergen skin testing should be considered in patients
with allergic rhinitis and asthma with persistent
symptoms to determine possible allergen triggers
Highly effective; disease modifying
Candidates
 Moderate to severe symptoms
 Lack of improvement with other modalities
 Presence of comorbid conditions
 Evidence of specific IgE sensitization based on testing
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Risk of anaphylaxis
Oral drops and low dose (provocation-neutralization
technique) immunotherapy have not been proven
effective in clinical studies
Impact of Immunotherapy on
Allergic Rhinitis Costs
4000
Dollars
Over 10
Years
3500
3000
2500
Rx
Rx + Imm 3 yrs
Rx + Imm 10 yrs
2000
1500
1000
500
0
Allergic Rhinitis
Sullivan in Current Views in… 1998
How early should we consider
Immunotherapy?
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Prevention of Asthma Onset
Preventive Allergy Treatment study in Northern
Europe:
 Development of new allergies is decreased and the
progression to asthma is decreased
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50% reduction in asthma in children with moderate to
severe allergic rhinitis who received IT compared to those
without IT
Moller C. et al, JACI 2002;109:251-256
How early should we consider
Immunotherapy?
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Prevention of New Sensitizations in children
22 children with HDM allergy only
 IT for 3 years with HDM extract
PTs New Sensitivities
None cat dog Alt Grass
IT 22
10 6 4
2 1
Con 22 0
12 8 6 6
p<.001
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A Des Roches, et al. JACI 1997; 99:450
How early should we consider
Immunotherapy?
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Prevention of New Sensitizations
GB Pajno, et al. Clin Exp Allergy 2001;31:1392-7
 F Purello-D’Ambrosio, et al. Clin Exp Allergy
2001;31:1295-1302
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Key Advances in Immunotherapy
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IT in children with only AR decreases asthma
Decreases bronchial hyper-responsiveness to
methacholine
Reduces risk of developing new allergies
Routine series is for 3-5 years
Gives long lasting relief of symptoms
High-dose sublingual IT appears to be safe but less
effective than injections and cost savings aren’t clear
because of amount of extract required
Allergy Prevention Strategies
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Promote breast feeding
Discourage early introduction of solid and
“at risk” food (milk, eggs, peanuts, seafood, ?
meats)
Reduce dust mite levels in homes
Avoid exposure to animal dander
Screen for allergy at all routine exams
Encourage awareness of allergen control
measures at work, school, and daycare
Consultation with Specialist
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Identification of allergic / non-allergic triggers
Education in allergen avoidance and control
If allergen immunotherapy is a consideration
If patient’s quality of life is significantly affected
Co-morbidities: asthma, recurrent sinusitis / OM,
nasal polyps
Duration of rhinitis > 3 months and / or requires
systemic corticosteroids to manage
Poor control – persistent symptoms