ALLERGIC DISEASES. BRONCHIAL ASTHMA

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ALLERGIC DISEASES.BRONCHIAL ASTHMA
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• 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.

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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.

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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).

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Antibody classes have distinct and overlapping
functions
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IgE complete structure
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Entire Ig structure
E
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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.

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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.

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• 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
  ß2-agonists
• - FEV 80 of normal,
• decr. 20-30.

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• 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
  ß2-agonists
• - FEV 60-80 of normal,
• decr. gt 30.

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• Stage 4. Severe-persistent bronchial asthma
• Clinical symptoms before treatment
• - persistent symptoms
• - frequent exacerbations
• - persistent night asthma symptoms
• - symptoms require everyday applying of
  ß2-agonists, shortening of fisical activity
• - FEV lt 60 of normal,
• decr. gt 30.

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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.

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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.

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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.

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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.

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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.

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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.

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spirography
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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.

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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

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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.

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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.)

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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.

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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.

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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.

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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 5-lipoxygenase

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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.

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THERAPY
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Allergists 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