ALLERGIC DISEASES. BRONCHIAL ASTHMA

1. ALLERGIC DISEASES.BRONCHIAL ASTHMA

2. 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 orasthma eqiuvalents on the background of extrapulmonary signs of allergy, family allerig anamnesis, eosiniphyl rate increasing in blood and sputum.

3. 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.[

4. 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).

6. Immunoglobulin classes

7. Antibody classes have distinct and overlapping functions

8. IgE complete structure

9. Entire Ig structure E

10. 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.

12. Clinical classification ofbronchial 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%.

13. Stage2. 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 β2-agonists; - FEV: 80% of normal, decr. 20-30%.

14. Stage3. 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 β2-agonists; - FEV: 60-80% of normal, decr. > 30%.

15. Stage4. 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%.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

22. spirography

23. 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.

24. 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

25. 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.

26. 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.)

27. 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.

28. 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.

29. 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.

30. 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

31. 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.

43. THERAPY

44. 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