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.

EPIDEMIOLOGEPIDEMIOLOGYY

Asthma is a common disease affecting 5% to 8% of the Asthma is a common disease affecting 5% to 8% of the population, or about 14 to 15 million people population, or about 14 to 15 million people in the in the USUSAA. . With 5 million children afflicted, it is the most common With 5 million children afflicted, it is the most common chronic disease of childhood. Despite all we know about chronic disease of childhood. Despite all we know about the pathogenesis and treatment of asthma, the the pathogenesis and treatment of asthma, the prevalence of and mortality from this condition have prevalence of and mortality from this condition have increased. From 1982 to increased. From 1982 to 2002002 the annual age-adjusted 2 the annual age-adjusted prevalence rose from 34.7 to 49.4 per 1,000 people, an prevalence rose from 34.7 to 49.4 per 1,000 people, an increase of 42%; the annual age-adjusted death rate for increase of 42%; the annual age-adjusted death rate for asthma rose 40% over this same period.Worldwide asthma rose 40% over this same period.Worldwide epidemiologic studies suggest that a large proportion of epidemiologic studies suggest that a large proportion of asthmatic people, particularly children, are also atopic.[ asthmatic people, particularly children, are also atopic.[

Allergic SensitizationAllergic SensitizationAllergic SensitizationAllergic Sensitization -- Allergens are internalized by -- Allergens are internalized by antigen-presenting cells (macrophages, dendritic cells, antigen-presenting cells (macrophages, dendritic cells, Langerhans cells) Langerhans cells) (A)(A) and degraded by proteolytic and degraded by proteolytic enzymes in phagolysosomes enzymes in phagolysosomes (B)(B), followed by , followed by intracellular association of allergen peptides and major intracellular association of allergen peptides and major histocompatibility complex (MHC) molecules histocompatibility complex (MHC) molecules (C)(C). . Complexes of MHC molecules and allergen peptides Complexes of MHC molecules and allergen peptides then move to the cell surface then move to the cell surface (D)(D). When a T helper cell . When a T helper cell receptor recognizes an allergen, it does so by binding receptor recognizes an allergen, it does so by binding simultaneously to the MHC molecule and to the allergen simultaneously to the MHC molecule and to the allergen partially surrounded by the MHC molecule partially surrounded by the MHC molecule (E)(E). . Interleukin-4 and other cytokines are then secreted by T Interleukin-4 and other cytokines are then secreted by T helper cells helper cells (F)(F), ultimately leading to the production of , ultimately leading to the production of specific IgE by B lymphocytes specific IgE by B lymphocytes (G)(G). The specific IgE then . The specific IgE then attaches to mast cells and other cells (basophils and attaches to mast cells and other cells (basophils and eosinophils), completing the process of sensitization eosinophils), completing the process of sensitization (H)(H). .

Immunoglobulin classes

Antibody classes have distinct and overlapping functions

IgE complete structureIgE complete structure

Entire Ig structureEntire Ig structureE

Symptomatic Symptomatic Early Allergic ResponseEarly Allergic Response

-- The C terminus (Fc portions) of IgE molecules -- The C terminus (Fc portions) of IgE molecules binds avidly to mast cells and basophils through binds avidly to mast cells and basophils through specific cell-surface receptors. When allergen specific cell-surface receptors. When allergen molecules contact surface-bound IgE, they molecules contact surface-bound IgE, they cause cross-linking of the IgE and subsequent cause cross-linking of the IgE and subsequent degranulation of the mast cells and basophils, degranulation of the mast cells and basophils, with the release of preformed mediators with the release of preformed mediators (histamine), newly generated mediators (histamine), newly generated mediators (prostaglandins, leukotrienes, and (prostaglandins, leukotrienes, and thromboxanes), and other inflammatory thromboxanes), and other inflammatory mediators. mediators.

Clinical classification ofClinical classification of bronchial asthma

StageStage 1. 1. Intermittent bronchial asthmaIntermittent bronchial asthmaClinical symptoms before treatment:Clinical symptoms before treatment: - - short-term symptoms less than once per month;short-term symptoms less than once per month; - - short-term exacerbations short-term exacerbations ((several hours – several daysseveral hours – several days));; - - night asthma symptoms less than 2 times per month;night asthma symptoms less than 2 times per month; - - absence of symptoms and normal lung function between absence of symptoms and normal lung function between

exacerbations;exacerbations; - - FEV: normal,FEV: normal, decr. lessdecr. less 20 20%.%.

StageStage 22. . Mild-persistent bronchial asthmaMild-persistent bronchial asthma

Clinical symptoms before treatment:Clinical symptoms before treatment:

- - symptoms once per day – once per month;symptoms once per day – once per month;

- - exacerbations could disturb activity and exacerbations could disturb activity and sleeping;sleeping;

- - night asthma symptoms 2-4 times per month;night asthma symptoms 2-4 times per month;

- - symptoms require everyday applying of symptoms require everyday applying of ββ2-2-agonistsagonists;;

- - FEV: 80% of normal,FEV: 80% of normal,

decr. decr. 2020-30%. -30%.

StageStage 33. . Moderate-persistent bronchial asthmaModerate-persistent bronchial asthma

Clinical symptoms before treatment:Clinical symptoms before treatment:

- - everyday symptoms;everyday symptoms;

- - exacerbations disturb activity and sleeping;exacerbations disturb activity and sleeping;

- - night asthma symptoms more than 1 per week;night asthma symptoms more than 1 per week;

- - symptoms require everyday applying of symptoms require everyday applying of ββ2-2-agonistsagonists;;

- - FEV: 60-80% of normal,FEV: 60-80% of normal,

decr. decr. > > 30%.30%.

StageStage 44. . Severe-persistent bronchial Severe-persistent bronchial asthmaasthma

Clinical symptoms before treatment:Clinical symptoms before treatment: - - persistent symptoms;persistent symptoms; - - frequent exacerbations;frequent exacerbations; - - persistent night asthma symptoms;persistent night asthma symptoms; - - symptoms require everyday applying of symptoms require everyday applying of

ββ2-2-agonists, shortening of fisical activityagonists, shortening of fisical activity;; - - FEV: < 60% of normal,FEV: < 60% of normal, decr. decr. > > 30%.30%.

Key Practice PointsKey Practice Points

Successful implementation of specific environmental Successful implementation of specific environmental measures can reduce airway inflammation, asthma measures can reduce airway inflammation, asthma symptoms, and the need for medical therapy. symptoms, and the need for medical therapy.

*** *** When pharmacotherapy is needed, a step-up approach When pharmacotherapy is needed, a step-up approach -- based on episode severity and frequency -- is -- based on episode severity and frequency -- is recommended. recommended.

*** *** Recent evidence suggests that specific immunotherapy Recent evidence suggests that specific immunotherapy improves asthma symptoms overall, with significant improves asthma symptoms overall, with significant reductions in medication and bronchial reductions in medication and bronchial hyperresponsiveness, but with only modest benefits on hyperresponsiveness, but with only modest benefits on pulmonary function.pulmonary function.

Evaluating the PatientEvaluating the Patient

The historyThe history. Evaluation begins with a careful allergy/environmental history to . Evaluation begins with a careful allergy/environmental history to identify exposures and triggers. The clinical history should include (1) the identify exposures and triggers. The clinical history should include (1) the nature of the illness/symptoms; (2) precipitators and alleviators of nature of the illness/symptoms; (2) precipitators and alleviators of symptoms; (3) the frequency and duration of attacks; (4) time lost from symptoms; (3) the frequency and duration of attacks; (4) time lost from school or work; (5) prior evaluation and treatment; (6) medical history; (7) school or work; (5) prior evaluation and treatment; (6) medical history; (7) family history; (8) past and current medications; and (9) occupation and family history; (8) past and current medications; and (9) occupation and hobbies. The environmental history should elicit information about these hobbies. The environmental history should elicit information about these four areas: four areas: The home: type, location, age, construction material; number of people in The home: type, location, age, construction material; number of people in residence; heating and cooling systems (air conditioners, fans, residence; heating and cooling systems (air conditioners, fans, dehumidifiers, humidifiers, air purifiers); flooring (carpets); pets (types, dehumidifiers, humidifiers, air purifiers); flooring (carpets); pets (types, habitat, duration in residence); pests habitat, duration in residence); pests The bedroom: location; condition; types of bed/bedding, flooring, furniture; The bedroom: location; condition; types of bed/bedding, flooring, furniture; contents of closets; presence of window dressings and other dust collectors contents of closets; presence of window dressings and other dust collectors General irritants: smokers in the home (how many, smoking allowed General irritants: smokers in the home (how many, smoking allowed inside?); mold or mildew; use of aerosol sprays inside?); mold or mildew; use of aerosol sprays Landscaping: amount of vegetation; types of grass, trees, flowers, shrubs; Landscaping: amount of vegetation; types of grass, trees, flowers, shrubs; exposure.exposure.

Allergy testingAllergy testing..

Before initiating certain environmental control Before initiating certain environmental control measures that may be cumbersome (eg, measures that may be cumbersome (eg, removing carpeting), expensive (eg, installing removing carpeting), expensive (eg, installing dehumidifiers), emotionally painful (eg, removing dehumidifiers), emotionally painful (eg, removing a loved pet from the home), or unnecessary (eg, a loved pet from the home), or unnecessary (eg, medications or immunotherapy), it is important to medications or immunotherapy), it is important to pinpoint the allergic triggers. Allergy testing is pinpoint the allergic triggers. Allergy testing is the only reliable method for determining the only reliable method for determining sensitivity to specific allergens. Its aim is to sensitivity to specific allergens. Its aim is to demonstrate allergen-specific IgE, which can be demonstrate allergen-specific IgE, which can be accomplished by skin testing or by serologic accomplished by skin testing or by serologic evaluation.evaluation.

Skin testingSkin testing

Direct introduction of antigen into the skin of the patient, Direct introduction of antigen into the skin of the patient, via the skin prick test (SPT), is the most common via the skin prick test (SPT), is the most common method of assessing sensitivity to a specific allergen. A method of assessing sensitivity to a specific allergen. A drop of potent extract is placed on the skin of the volar drop of potent extract is placed on the skin of the volar aspect of the forearm or back, followed by a prick or aspect of the forearm or back, followed by a prick or scratch, which exposes the allergen to the mast cells scratch, which exposes the allergen to the mast cells located just under the stratum corneum. The classic located just under the stratum corneum. The classic wheal and flare reaction defines a positive test. In some wheal and flare reaction defines a positive test. In some cases, the SPT may be followed by an intracutaneous cases, the SPT may be followed by an intracutaneous (intradermal) injection of extract. Compared with the (intradermal) injection of extract. Compared with the SPT, the intradermal injection method has a higher SPT, the intradermal injection method has a higher sensitivity but a lower specificity. Furthermore, because sensitivity but a lower specificity. Furthermore, because of a larger antigen challenge, it may increase the risk of of a larger antigen challenge, it may increase the risk of a systemic reaction.a systemic reaction.

Serologic testingSerologic testing

Certain circumstances preclude the use of Certain circumstances preclude the use of skin testing, including extraordinary skin testing, including extraordinary sensitivity to a suspected allergen, the use sensitivity to a suspected allergen, the use of antihistamines or ß blockers, of antihistamines or ß blockers, pregnancy, dermatographism, or other pregnancy, dermatographism, or other skin abnormalities that would prevent the skin abnormalities that would prevent the placement of the SPT. In such situations, placement of the SPT. In such situations, serologic studies for allergy can be serologic studies for allergy can be performed.performed.

spirographyspirography

In addition to the history and physical examination, an In addition to the history and physical examination, an objective measurement of lung function by simple objective measurement of lung function by simple pulmonary function studies helps to confirm a diagnosis pulmonary function studies helps to confirm a diagnosis of asthma as well as to establish response to therapy. of asthma as well as to establish response to therapy. The most common and important indices of expiratory The most common and important indices of expiratory flow are: flow are: Forced expiratory volume in 1 second (FEV1): the Forced expiratory volume in 1 second (FEV1): the maximum volume of air expired in 1 second from full maximum volume of air expired in 1 second from full inspiration (total lung capacity [TLC]) to complete inspiration (total lung capacity [TLC]) to complete exhalation (residual volume [RV]); and, exhalation (residual volume [RV]); and, Peak expiratory flow (PEF): the maximum flow that can Peak expiratory flow (PEF): the maximum flow that can be generated during a forced expiratory maneuver. be generated during a forced expiratory maneuver. The forced vital capacity (FVC) maneuver (simple The forced vital capacity (FVC) maneuver (simple spirogram) may be graphically displayed either as a spirogram) may be graphically displayed either as a volume-time curve or as a flow-volume loop. volume-time curve or as a flow-volume loop.

spirographyspirography

Making the diagnosisMaking the diagnosis

Once allergen sensitivity is identified, it is Once allergen sensitivity is identified, it is important to decide on its clinical significance in important to decide on its clinical significance in the context of the patient's history. A diagnosis the context of the patient's history. A diagnosis of allergy rests on three observations: (1) a of allergy rests on three observations: (1) a suggestive history with symptoms in a target suggestive history with symptoms in a target organ such as the nose or lower respiratory organ such as the nose or lower respiratory tract; (2) the demonstration of allergen-specific tract; (2) the demonstration of allergen-specific IgE; and (3) the occurrence or aggravation of IgE; and (3) the occurrence or aggravation of symptoms in the target organ when a patient is symptoms in the target organ when a patient is exposed to the implicated allergen.exposed to the implicated allergen.

Four key components Four key components of asthma therapyof asthma therapy

Patient education and self-management Patient education and self-management Objective assessment of lung function and Objective assessment of lung function and disease severity, including home PEF disease severity, including home PEF monitoring monitoring Environmental control with avoidance of Environmental control with avoidance of asthma triggers asthma triggers Pharmacologic therapy Pharmacologic therapy

Abbreviations: PEF, peak expiratory flowAbbreviations: PEF, peak expiratory flow

specific immunotherapy (SIT) specific immunotherapy (SIT) Identify specific allergens Identify specific allergens Establish the presence of IgE antibodies Establish the presence of IgE antibodies Confirm that symptoms emerge upon allergen exposure Confirm that symptoms emerge upon allergen exposure Confirm the efficacy of immunotherapy for the specific Confirm the efficacy of immunotherapy for the specific allergens allergens Assess the severity and duration of asthma symptoms Assess the severity and duration of asthma symptoms Characterize additional triggers Characterize additional triggers Assess prior response to nonimmunologic therapy Assess prior response to nonimmunologic therapy Ascertain the availability of standardized or high-quality Ascertain the availability of standardized or high-quality extracts extracts Assess possible contraindications to immunotherapy Assess possible contraindications to immunotherapy Analyze sociologic factors that may affect Analyze sociologic factors that may affect immunotherapy. immunotherapy.

BronchodilatorsBronchodilators

Inhaled ß agonistsInhaled ß agonists. Short-acting inhaled ß-adrenergic . Short-acting inhaled ß-adrenergic agonists are the "rescue" agents of choice for agonists are the "rescue" agents of choice for symptomatic relief from acute bronchospasm. These symptomatic relief from acute bronchospasm. These agents act via a G-protein-linked receptor on airway agents act via a G-protein-linked receptor on airway smooth muscle cells to stimulate adenylyl cyclase and smooth muscle cells to stimulate adenylyl cyclase and increase cyclic adenosine monophosphate. Beta agonists increase cyclic adenosine monophosphate. Beta agonists also inhibit mediator release from inflammatory cells and also inhibit mediator release from inflammatory cells and improve mucociliary clearance. Three ß2-selective improve mucociliary clearance. Three ß2-selective agonists -- albuterol, metaproterenol, and terbutaline -- agonists -- albuterol, metaproterenol, and terbutaline -- are among the most commonly used antiasthma agents are among the most commonly used antiasthma agents (Salmeterol, a long-acting inhaled ß agonist, has a clinical (Salmeterol, a long-acting inhaled ß agonist, has a clinical effect that lasts 12 hours or more. Its long onset of action effect that lasts 12 hours or more. Its long onset of action precludes its use as a rescue agent.)precludes its use as a rescue agent.)

Inhaled anticholinergicsInhaled anticholinergics

Anticholinergics have been used for centuries to Anticholinergics have been used for centuries to treat asthma. These drugs block the treat asthma. These drugs block the parasympathetic postganglionic muscarinic parasympathetic postganglionic muscarinic receptors found primarily in the proximal receptors found primarily in the proximal airways, resulting in bronchodilatation. Because airways, resulting in bronchodilatation. Because of their low systemic absorption, inhaled of their low systemic absorption, inhaled anticholinergics such as ipratropium bromide anticholinergics such as ipratropium bromide have few side effects. The role of these drugs in have few side effects. The role of these drugs in both the stable and aggravated asthmatic states both the stable and aggravated asthmatic states has yet to be fully defined, however. has yet to be fully defined, however.

TheophyllineTheophylline

The use of theophylline, once a mainstay of The use of theophylline, once a mainstay of asthma therapy, has waned. Although this drug asthma therapy, has waned. Although this drug is a useful bronchodilator, it is not as potent as is a useful bronchodilator, it is not as potent as the inhaled ß agonists. In addition, it has a the inhaled ß agonists. In addition, it has a narrow therapeutic window and its metabolism is narrow therapeutic window and its metabolism is affected by other drugs and disease states, affected by other drugs and disease states, which can make proper dosing difficult. It may be which can make proper dosing difficult. It may be used as a sustained-release product for used as a sustained-release product for prolonged symptomatic relief. This drug is an prolonged symptomatic relief. This drug is an option for some patients because of its low cost option for some patients because of its low cost and its availability in oral (as opposed to and its availability in oral (as opposed to inhalational) form.inhalational) form.

Cromolyn sodium and Cromolyn sodium and nedocromil sodiumnedocromil sodium

These drugs exert antiinflammatory, but These drugs exert antiinflammatory, but not bronchodilatory, effects. Their not bronchodilatory, effects. Their mechanism of action remains unclear, mechanism of action remains unclear, although they seem to inhibit the actions of although they seem to inhibit the actions of a variety of inflammatory cells. They are a variety of inflammatory cells. They are useful in controlling mild to moderate useful in controlling mild to moderate asthma symptoms and are favored in asthma symptoms and are favored in children because they have few unwanted children because they have few unwanted effects. effects.

Antileukotriene agentsAntileukotriene agents

Leukotrienes play a significant role in the Leukotrienes play a significant role in the pathogenesis of asthma. They are potent pathogenesis of asthma. They are potent bronchoconstrictors, increasing airway reactivity bronchoconstrictors, increasing airway reactivity in asthmatic patients and inducing an influx of in asthmatic patients and inducing an influx of eosinophils and neutrophils into the asthmatic eosinophils and neutrophils into the asthmatic airway. They are also potent secretagogues of airway. They are also potent secretagogues of mucus and they increase vascular permeability mucus and they increase vascular permeability and thus airway edema. Data also support a role and thus airway edema. Data also support a role for leukotrienes in the pathogenesis of the for leukotrienes in the pathogenesis of the allergic nasal response.[20] The cysteinyl allergic nasal response.[20] The cysteinyl leukotrienes (cysLT) C4, D4, and E4 are derived leukotrienes (cysLT) C4, D4, and E4 are derived from the metabolism of arachidonic acid by 5-from the metabolism of arachidonic acid by 5-lipoxygenase lipoxygenase

Inhaled corticosteroidsInhaled corticosteroidsThese are potent antiinflammatory medications These are potent antiinflammatory medications that have a broad effect on the inflammatory that have a broad effect on the inflammatory cascade: they suppress both T- and B-cell cascade: they suppress both T- and B-cell function; inhibit inflammatory cell effector function; inhibit inflammatory cell effector functions such as adhesion, chemotaxis, and functions such as adhesion, chemotaxis, and phagocytosis; and inhibit mediator production. phagocytosis; and inhibit mediator production. Corticosteroids also up-regulate the expression Corticosteroids also up-regulate the expression and affinity of the ß2 receptor and thus augment and affinity of the ß2 receptor and thus augment the action of ß agonists. Systemic the action of ß agonists. Systemic corticosteroids, unlike inhaled corticosteroids, corticosteroids, unlike inhaled corticosteroids, are associated with many adverse effects and are associated with many adverse effects and are indicated only for the management of severe are indicated only for the management of severe exacerbations. exacerbations.

THERAPYTHERAPY

AllergistAllergist’s consulting is needfull’s consulting is needfull

Is not meeting goals of therapy Is not meeting goals of therapy Has moderate/severe persistent asthma Has moderate/severe persistent asthma Has mild persistent asthma (infant or young child) Has mild persistent asthma (infant or young child) Has experienced a near-fatal asthma attack Has experienced a near-fatal asthma attack Requires continuous oral corticosteroids Requires continuous oral corticosteroids Requires frequent bursts of oral corticosteroids Requires frequent bursts of oral corticosteroids Requires high-dose inhaled corticosteroids Requires high-dose inhaled corticosteroids Has atypical signs or symptoms Has atypical signs or symptoms Has symptoms likely to have been precipitated by an Has symptoms likely to have been precipitated by an occupational/environmental inhalant occupational/environmental inhalant Is a candidate for immunotherapy Is a candidate for immunotherapy Requires additional education about his or her conditionRequires additional education about his or her condition