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ALLERGIC DISEASES.
BRONCHIAL ASTHMA
BRONCHIAL ASTHMA – chronic
immune inflammatory process with
changed reactivity of bronches that is
characterized by bronchial reactivity
changes and has a clinical symptoms of
totally reversed expiratory dyspnoe,
asthma status or asthma eqiuvalents on
the background of extrapulmonary signs
of allergy, family allerig anamnesis,
eosiniphyl rate increasing in blood and
sputum.
EPIDEMIOLOGY
Asthma is a common disease affecting 5% to 8% of the
population, or about 14 to 15 million people in the USA.
With 5 million children afflicted, it is the most common
chronic disease of childhood. Despite all we know about
the pathogenesis and treatment of asthma, the
prevalence of and mortality from this condition have
increased. From 1982 to 2002 the annual age-adjusted
prevalence rose from 34.7 to 49.4 per 1,000 people, an
increase of 42%; the annual age-adjusted death rate for
asthma rose 40% over this same period.Worldwide
epidemiologic studies suggest that a large proportion of
asthmatic people, particularly children, are also atopic.[
Allergic Sensitization
Allergic Sensitization -- Allergens are internalized by
antigen-presenting cells (macrophages, dendritic cells,
Langerhans cells) (A) and degraded by proteolytic
enzymes in phagolysosomes (B), followed by
intracellular association of allergen peptides and major
histocompatibility complex (MHC) molecules (C).
Complexes of MHC molecules and allergen peptides
then move to the cell surface (D). When a T helper cell
receptor recognizes an allergen, it does so by binding
simultaneously to the MHC molecule and to the allergen
partially surrounded by the MHC molecule (E).
Interleukin-4 and other cytokines are then secreted by T
helper cells (F), ultimately leading to the production of
specific IgE by B lymphocytes (G). The specific IgE then
attaches to mast cells and other cells (basophils and
eosinophils), completing the process of sensitization (H).
Immunoglobulin classes
Antibody classes have distinct and overlapping functions
IgE complete structure
Entire Ig structure
E
Symptomatic
Early Allergic Response
-- The C terminus (Fc portions) of IgE molecules
binds avidly to mast cells and basophils through
specific cell-surface receptors. When allergen
molecules contact surface-bound IgE, they
cause cross-linking of the IgE and subsequent
degranulation of the mast cells and basophils,
with the release of preformed mediators
(histamine), newly generated mediators
(prostaglandins, leukotrienes, and
thromboxanes), and other inflammatory
mediators.
Clinical classification of
bronchial asthma
Stage 1. Intermittent bronchial asthma
Clinical symptoms before treatment:
- short-term symptoms less than once per month;
- short-term exacerbations (several hours – several days);
- night asthma symptoms less than 2 times per month;
- absence of symptoms and normal lung function between
exacerbations;
- FEV: normal,
decr. less 20%.
Stage 2. Mild-persistent bronchial asthma
Clinical symptoms before treatment:
- symptoms once per day – once per month;
- exacerbations could disturb activity and
sleeping;
- night asthma symptoms 2-4 times per month;
- symptoms require everyday applying of β2agonists;
- FEV: 80% of normal,
decr. 20-30%.
Stage 3. Moderate-persistent bronchial asthma
Clinical symptoms before treatment:
- everyday symptoms;
- exacerbations disturb activity and sleeping;
- night asthma symptoms more than 1 per week;
- symptoms require everyday applying of β2agonists;
- FEV: 60-80% of normal,
decr. > 30%.
Stage 4. Severe-persistent bronchial
asthma
Clinical symptoms before treatment:
- persistent symptoms;
- frequent exacerbations;
- persistent night asthma symptoms;
- symptoms require everyday applying of
β2-agonists, shortening of fisical activity;
- FEV: < 60% of normal,
decr. > 30%.
Key Practice Points
Successful implementation of specific environmental
measures can reduce airway inflammation, asthma
symptoms, and the need for medical therapy.
***
When pharmacotherapy is needed, a step-up approach - based on episode severity and frequency -- is
recommended.
***
Recent evidence suggests that specific immunotherapy
improves asthma symptoms overall, with significant
reductions in medication and bronchial
hyperresponsiveness, but with only modest benefits on
pulmonary function.
Evaluating the Patient
The history. Evaluation begins with a careful allergy/environmental history to
identify exposures and triggers. The clinical history should include (1) the
nature of the illness/symptoms; (2) precipitators and alleviators of
symptoms; (3) the frequency and duration of attacks; (4) time lost from
school or work; (5) prior evaluation and treatment; (6) medical history; (7)
family history; (8) past and current medications; and (9) occupation and
hobbies. The environmental history should elicit information about these
four areas:
The home: type, location, age, construction material; number of people in
residence; heating and cooling systems (air conditioners, fans,
dehumidifiers, humidifiers, air purifiers); flooring (carpets); pets (types,
habitat, duration in residence); pests
The bedroom: location; condition; types of bed/bedding, flooring, furniture;
contents of closets; presence of window dressings and other dust collectors
General irritants: smokers in the home (how many, smoking allowed
inside?); mold or mildew; use of aerosol sprays
Landscaping: amount of vegetation; types of grass, trees, flowers, shrubs;
exposure.
Allergy testing.
Before initiating certain environmental control
measures that may be cumbersome (eg,
removing carpeting), expensive (eg, installing
dehumidifiers), emotionally painful (eg, removing
a loved pet from the home), or unnecessary (eg,
medications or immunotherapy), it is important to
pinpoint the allergic triggers. Allergy testing is
the only reliable method for determining
sensitivity to specific allergens. Its aim is to
demonstrate allergen-specific IgE, which can be
accomplished by skin testing or by serologic
evaluation.
Skin testing
Direct introduction of antigen into the skin of the patient,
via the skin prick test (SPT), is the most common
method of assessing sensitivity to a specific allergen. A
drop of potent extract is placed on the skin of the volar
aspect of the forearm or back, followed by a prick or
scratch, which exposes the allergen to the mast cells
located just under the stratum corneum. The classic
wheal and flare reaction defines a positive test. In some
cases, the SPT may be followed by an intracutaneous
(intradermal) injection of extract. Compared with the
SPT, the intradermal injection method has a higher
sensitivity but a lower specificity. Furthermore, because
of a larger antigen challenge, it may increase the risk of
a systemic reaction.
Serologic testing
Certain circumstances preclude the use of
skin testing, including extraordinary
sensitivity to a suspected allergen, the use
of antihistamines or ß blockers,
pregnancy, dermatographism, or other skin
abnormalities that would prevent the
placement of the SPT. In such situations,
serologic studies for allergy can be
performed.
spirography
In addition to the history and physical examination, an
objective measurement of lung function by simple
pulmonary function studies helps to confirm a diagnosis
of asthma as well as to establish response to therapy.
The most common and important indices of expiratory
flow are:
Forced expiratory volume in 1 second (FEV1): the
maximum volume of air expired in 1 second from full
inspiration (total lung capacity [TLC]) to complete
exhalation (residual volume [RV]); and,
Peak expiratory flow (PEF): the maximum flow that can
be generated during a forced expiratory maneuver.
The forced vital capacity (FVC) maneuver (simple
spirogram) may be graphically displayed either as a
volume-time curve or as a flow-volume loop.
spirography
Making the diagnosis
Once allergen sensitivity is identified, it is
important to decide on its clinical significance in
the context of the patient's history. A diagnosis of
allergy rests on three observations: (1) a
suggestive history with symptoms in a target
organ such as the nose or lower respiratory
tract; (2) the demonstration of allergen-specific
IgE; and (3) the occurrence or aggravation of
symptoms in the target organ when a patient is
exposed to the implicated allergen.
Four key components
of asthma therapy
Patient education and self-management
Objective assessment of lung function and
disease severity, including home PEF
monitoring
Environmental control with avoidance of
asthma triggers
Pharmacologic therapy
Abbreviations: PEF, peak expiratory flow
specific immunotherapy (SIT)
Identify specific allergens
Establish the presence of IgE antibodies
Confirm that symptoms emerge upon allergen exposure
Confirm the efficacy of immunotherapy for the specific
allergens
Assess the severity and duration of asthma symptoms
Characterize additional triggers
Assess prior response to nonimmunologic therapy
Ascertain the availability of standardized or high-quality
extracts
Assess possible contraindications to immunotherapy
Analyze sociologic factors that may affect
immunotherapy.
Bronchodilators
Inhaled ß agonists. Short-acting inhaled ß-adrenergic
agonists are the "rescue" agents of choice for
symptomatic relief from acute bronchospasm. These
agents act via a G-protein-linked receptor on airway
smooth muscle cells to stimulate adenylyl cyclase and
increase cyclic adenosine monophosphate. Beta agonists
also inhibit mediator release from inflammatory cells and
improve mucociliary clearance. Three ß2-selective
agonists -- albuterol, metaproterenol, and terbutaline -are among the most commonly used antiasthma agents
(Salmeterol, a long-acting inhaled ß agonist, has a clinical
effect that lasts 12 hours or more. Its long onset of action
precludes its use as a rescue agent.)
Inhaled anticholinergics
Anticholinergics have been used for centuries to
treat asthma. These drugs block the
parasympathetic postganglionic muscarinic
receptors found primarily in the proximal
airways, resulting in bronchodilatation. Because
of their low systemic absorption, inhaled
anticholinergics such as ipratropium bromide
have few side effects. The role of these drugs in
both the stable and aggravated asthmatic states
has yet to be fully defined, however.
Theophylline
The use of theophylline, once a mainstay of
asthma therapy, has waned. Although this drug
is a useful bronchodilator, it is not as potent as
the inhaled ß agonists. In addition, it has a
narrow therapeutic window and its metabolism is
affected by other drugs and disease states,
which can make proper dosing difficult. It may be
used as a sustained-release product for
prolonged symptomatic relief. This drug is an
option for some patients because of its low cost
and its availability in oral (as opposed to
inhalational) form.
Cromolyn sodium and
nedocromil sodium
These drugs exert antiinflammatory, but
not bronchodilatory, effects. Their
mechanism of action remains unclear,
although they seem to inhibit the actions of
a variety of inflammatory cells. They are
useful in controlling mild to moderate
asthma symptoms and are favored in
children because they have few unwanted
effects.
Antileukotriene agents
Leukotrienes play a significant role in the
pathogenesis of asthma. They are potent
bronchoconstrictors, increasing airway reactivity
in asthmatic patients and inducing an influx of
eosinophils and neutrophils into the asthmatic
airway. They are also potent secretagogues of
mucus and they increase vascular permeability
and thus airway edema. Data also support a role
for leukotrienes in the pathogenesis of the
allergic nasal response.[20] The cysteinyl
leukotrienes (cysLT) C4, D4, and E4 are derived
from the metabolism of arachidonic acid by 5lipoxygenase
Inhaled corticosteroids
These are potent antiinflammatory medications
that have a broad effect on the inflammatory
cascade: they suppress both T- and B-cell
function; inhibit inflammatory cell effector
functions such as adhesion, chemotaxis, and
phagocytosis; and inhibit mediator production.
Corticosteroids also up-regulate the expression
and affinity of the ß2 receptor and thus augment
the action of ß agonists. Systemic
corticosteroids, unlike inhaled corticosteroids,
are associated with many adverse effects and
are indicated only for the management of severe
exacerbations.
THERAPY
Allergist’s consulting is needfull
Is not meeting goals of therapy
Has moderate/severe persistent asthma
Has mild persistent asthma (infant or young child)
Has experienced a near-fatal asthma attack
Requires continuous oral corticosteroids
Requires frequent bursts of oral corticosteroids
Requires high-dose inhaled corticosteroids
Has atypical signs or symptoms
Has symptoms likely to have been precipitated by an
occupational/environmental inhalant
Is a candidate for immunotherapy
Requires additional education about his or her condition