BRONCHIAL ASTHMA

Prof. Vatutin N.T.

Definition
Asthma is a chronic inflammatory disease of the airways which develops under the allergens influence, associates with bronchial hyperresponsiveness and reversible obstruction and manifests with attacks of dyspnea, breathlessness, cough, wheezing, chest tightness and sibilant rales more expressed at breathing-out.

Epidemiology
According to epidemiological studies asthma affects 1-18% of population of different countries. Only in 2006 more than 300 million patients suffered from asthma all over the world, 250 thousands of patients die of asthma. The incidence of asthma is higher in countries with increased air pollution.

Etiology
As asthma is a respiratory allergic disease, the influence of allergens permeated into the organism through airways is essential for the disease development.

The allergens are divided into: communal, industrial, occupational, natural pharmacological

ommunal allergens are contained in the air of apartment houses. They are: house-dust mites which live in carpets, mattresses and upholstered furniture; spittle, excrements, desquamated epidermis, hair and fur of domestic animals; vital products of domestic insects (e.g., cockroach); mycelial yeast-like fungi (molds); tobacco smoke during active or passive smoking; various communal aerosols and synthetic detergents.

Among the industrial allergens nitric, carbonic, sulfuric oxides, formaldehyde, ozone and emissions of biotechnological industry main components of industrial and photochemical smog - must be mentioned. The most important occupational allergens are dust of stock buildings, mills, weaving-mills, book depositories etc. Natural allergens are represented by plant pollen (especially ambrosia, wormwood and goose-foot pollen) and different respiratory, particularly viral, infections.

Some allergens which may cause asthma

House-dust mites which live in carpets, mattresses and upholstered furniture Spittle, excrements, hair and fur of domestic animals

Plant pollen
Dust of book depositories Pharmacological agents (enzymes, antibiotics, vaccines, serums) Food components (stabilizers, genetically modified products)

Genetic abnormalities which lead to excessive production of allergen-specific antibodies (Ig E) is called atopy - significant factor in asthma genesis in many patients. A lot of cases of atopy are inherited, and recent epidemiological studies showed steady increase in number of people with high serum level of Ig E. Trigger-factors, which provoke bronchospasm, are: a simultaneous penetration of a large quantity of allergen, viral respiratory infection, hyperventilation, physical exertion, emotional stress, becoming too cold, adverse weather conditions, administration of some medicines (aspirin, b-blockers).

Pathophysiology
Asthma pathophysiology is quite difficult and insufficiently studied. Undoubtedly, in most cases the disease is based on 1 type hypersensitivity reaction. The genesis of any allergic reaction may be divided into immune, pathochemical and pathophysiologic phases.

Allergens

Immune phase
B-cell T-cell

Allergen-specific IgE

After involving into the airways allergens activate immunocompetent cells. As a result Blymphocytes produce antibodies of Ig E class. In case of asthma T-lymphocytes are inhibited, so the activation of B-lympocytes and Ig E production are excessive, exceeding normal needs.

Further these antibodies bind to the surface of mast cells, basophils and eosinophils of bronchial mucous. When a new portion of allergen involves the respiratory system, it interacts with IgE-antibodies. This is a first, immune phase of allergic reaction.

As a result of antigen-antibody reaction the peculiar explosion occurs. The membranes of mast cells, basophils and eosinophils of bronchial mucous wreck with output of biologically active substances (histamine, serotonin, chemotaxis factors, heparin, proteases, thromboxane, leukotrienes, prostaglandins), Airway fill which induce hyperergic Muscles with mucus inflammation, mucous edema, contract spasm of smooth myocytes, glands hypersecretion, viscous exudate formation in bronchial lumen.
Airways swell

Pathochemical phase

Asthma exacerbation, occurring as a result, is a clinical manifestation of the 3rd, pathophysiological, phase of allergic reaction.
The indicated mechanism is specific for atopic (exogenous) asthma genesis. In addition to this,

autosensibilization of damaged pulmonary tissue, neuropsychic disturbances, corticoid insufficiency, adrenergic imbalance, impairment of arachidonic acid metabolism, genetic and some other factors
probably play a certain role in genesis of nonatopic (endogenous) asthma.

Pathologic anatomy
Macroscopic changes:
viscous mucous/ mucopurulent phlegm airway dyskinesia with zones of spastic contraction and paralytic expansion of bronchi obstruction of airway lumen

lung emphysema, pneumosclerosis RV and RA hypertrophy and dilation

Microscopic changes:
Bronchial wall infiltration with mast cells, eosinophils, basophils and T-lymphocytes Edema of mucous and submucous tunics Destruction of bronchial epithelium Hypertrophy of bronchial smooth muscles, Hyperplasy of submucous glands Microvessels dilation

Depending on etiology asthma is divided into exogenous (atopic) and endogenous (nonatopic). By clinical course asthma is divided into intermittent (beginning, early) and persistent (chronic, late). Depending on frequency of exacerbations, limitations of patients physical activity and lung function persistent asthma is divided into mild, moderate and severe (lung function is assessed by forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF) and daily variability of these parameters). There are also remission phase and exacerbations.

Classification

Asthma severity classification

Clinical course, severity Intermittent Daytime asthma symptoms

Nighttime awakenings 2 and < /month > 2 /month > 1 /week Daily

FEV1, PEF
>80% predicted. Daily variability < 20% >80% predicted. Daily variability 20-30% > 60 but < 80% predicted. Variability>30%. <60% predicted. Variability > 30%.

< 1 /week 1 /week but not daily Daily

Persistent, which limit normal activity

Mild persistent Moderate persistent Severe persistent

In recommendations of Global Initiative for Asthma (GINA) asthma is classified on the base of control assessment and is divided into well-controlled, partially controlled and uncontrolled. Asthma control is considered as: daytime symptoms 2 /week; ability to engage in normal daily activity; the absence of nighttime awakenings as a result of asthma symptoms; need in bronchodilators administration 2 /week; the absence of asthma exacerbations; normal or near normal lung function parameters.

Clinical manifestations

Classic signs and symptoms of asthma are: attacks of expiratory dyspnea shortness of breath cough chest tightness wheezing (high-pitched whistling sounds when breathing out) sibilant rales

In typical cases in development of asthma exacerbation there are 3 periods prodromal

period, the height period and the period of reverse changes.

At the prodromal period: vasomotoric nasal reaction with profuse watery discharge, sneezing, dryness in nasopharynx, paroxysmal cough with viscous sputum, emotional lability, excessive sweating, skin itch and other symptoms may occur.

At the peack of exacerbation there are:

expiratory dyspnea forced position with supporting on arms poorly productive cough cyanotic skin and mucous tunics hyperexpansion of thorax with use of all accessory muscles during breathing at lung percussion: tympanitis, shifted downward lung borders at auscultation: diminished breath sounds, sibilant rales, prolonged breathing-out, tachycardia. in severe exacerbations: the signs of right-sided heart failure (swollen neck veins, hepatomegalia), overload of right heart chambers on ECG.

At the period of the reverse changes, which comes spontaneously or under pharmacologic therapy, dyspnea and breathlessness relieve or disappear, sputum becomes not so viscous, cough turns to be productive, patient breathes easier.

The severe and prolonged asthma exacerbation with intensive progressive respiratory failure, hypoxemia, hypercapnia, respiratory acidosis, increased blood viscosity and the most important sign is blockade of bronchial b2-receptors. Stages: 1st - refractory response to b2-agonists (may be paradoxical reaction with bronchospasm aggravation) 2nd - silent lung because of severe bronchial obstruction and collapse of small and intermediate bronchi; 3rd stage the hypercapnic coma.

Asthmatic status

In many cases asthma, particularly intermittent, manifests with few and atypical signs: episodic appearance of wheezing; cough, heavy breathing occurring at night; cough, hoarseness after physical activity; seasonal cough, wheezing, chest tightness (e.g., during pollen period of ambrosia); the same symptoms occurring during contact with allergens, irritants; lingering course of acute respiratory infections.

Asthma complications
The complications of asthma exacerbations are: pneumothorax lung atelectasis pneumonia acute or subacute cor pulmonale asthmatic status. Persistent asthma causes: fibrosing bronchitis small bronchi deformation and obliteration emphysema pneumosclerosis, chronic respiratory failure chronic cor pulmonale.

Asthma in childhood leads to growth inhibition and thoracic deformation.

Investigations
Lab Data
Eosinophilia, moderate leukocytosis in blood count as well as increased serum level of Ig E can be found in patients with asthma, especially at asthma exacerbations. Inflammatory cells, Curschmann's spirals (viscous mucus which copies small bronchi) and Charcot-Leyden crystals (crystallized enzymes of eosinophils and mast cells) can be observed in sputum.

Chest X-ray reveals:

hyperlucency of lung fields low standing and limited mobility of diaphragm expanded intercostal spaces horizontal rib position.

ECG
especially in case of severe, persistent asthma, shows hypertrophy of right heart chambers.
Right axis deviation, Rs type complex in V1 lead, low amplitude R in V5-V6 leads

Lung function assessment

The diagnosis and severity assessment of asthma is based mainly on parameters of lung function. The most important of them are:

forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF), which

are measured during spirometry at forced breathing-out.

PEF

Expiration

FEF
FEF

Flow
Inspiration Volume

PIF

FEV1 and PEF directly depend on bronchial lumen size and elastic properties of surrounding lung tissue.

Increase in FEV1 and PEF after inhalation of bronchodilators (b2-agonists) of 15% and more is specific for asthma.

PEF also can be measured with the help of individual devices peak flow meters

Diagnosis
Typical clinical manifestations and lung function assessment are sufficient for diagnosis of asthma.

Differential diagnosis
Asthma is to be differentiated with a number of diseases manifesting with dyspnea cardiac, uremic, hysteric asthma, systemic vasculitis, bronchocarcinoma, carcinoid and chronic obstructive lung diseases.

In contrast to bronchial, in case of cardiac asthma

the signs of severe heart disease and pulmonary congestion can be found.

In case of uremic asthma severe renal pathology takes place as well as other manifestations of uremia. Dyspnea without bronchospasm is specific for hysteric asthma. In patients with systemic vasculitis fever, weight loss, impairment of other organs and nervous system, arterial hypertension, arthralgia, myalgia, specific changes in tissue sampling may be revealed. Carcinoid intestinal tumors manifest with watery excrements, rumbling, heat sensation in head, tricuspid valve damage. In differentiating of bronchospastic syndrome in bronchial tumors ray-path methods (X-ray, computer tomography, bronchography) and bronchoscopy are importantant.

includes:

Management

1. Avoiding the contact with allergen. If it is impossible, the specific hyposensitization with standard allergens should be performed. It is rather effective in case of monoallergy, in intermittent and mild persistent asthma, in remission phase. 2. Elimination of trigger factors (rational job placement, changing the residence, psychological and physical adaptation, careful drug using) is the second condition for successful asthma treatment.

3. Optimally selected medical care is the base of

asthma management.

Drug therapy
2 drug categories are used: Antiinflammatory drugs (basic) Are divided into: Bronchodilators 3 groups: b2-agonists anticholinergic drugs methylxanthines

hormone-containing (corticosteroids) nonhormone-containing (cromones, leukotriene receptor antagonists)

Corticosteroids
The working mechanism lays in:

Inhaled corticosteroids (beclamethazone,

cell membrane stabilization

inhibition of inflammatory mediators restoring the sensivity of b2-receptors.

inhacort, budesonide, flixotid, fluticazone, asmacort, asthmanex) are

the most effective and safe and considered to be the first line drugs for asthma treatment. Systemic are used during short courses, mainly in case of severe persistent asthma or asthmatic status.

Cromones
(cromolyn sodium intal, and nedocromil tiled)
stabilize cell membranes, used mainly in pediatric practice (in childhood) in case of intermittent or mild persistent asthma.

(montelukast, zafirlukast)
have the moderate intiinflammatory activity used in case of aspirininduced asthma and asthma of physical exertion.

Leukotriene receptor antagonists

Bronchodilators
b2-agonists
Stimulates b2-adrenergic

Anticholinergic drugs
reduce tonus of vagus

receptors of bronchi

Smooth muscle relaxation

Methylxanthines

inhibit phosphodiesterase

Inhaled b2-agonists are the basic drug group among bronchodilators.

Short-acting (duration of action 5-6 h) b2agonists - salbutamol, fenoterol - are used for quick relief of asthma symptoms. Long-acting (> 12 h) b2-agonists salmoterol, farmoterol - for prevention of asthma symptoms occurring.

Anticholinergic drugs (ipratropium bromide, atrovent, troventol) are used predominantly in nighttime asthma and in elderly patients because of the least cardiotoxic effect. Methylxanthines in comparison with other bronchodilators have the less bronchodilating potential. There are long-acting (>12 h) (theopec, theolong, theodur, euphilong) as well as short-acting (aminophylline, theophylline) drugs in this group.

Combined inhaled drugs (corticosteroids with b2agonists) seretid, simbicort with use of delivery devices (nebulasers, turbuhalers, spasers, spinhalers, sinchroners) enhance the effectiveness of asthma therapy.

Oxygen Systemic corticosteroids (Hydrocortisone 200mg or Methylprednisolone 125mg every 6h IV or Prednisolone 50 mg/day per os) Inhalations of short-acting b2-agonists Salbutamol 5mg or Fenoterol 2mg through nebulaser 3 times at 1st hour, then once an hour till distinct improvement of patients condition is achieved; then 3-4 times a day. Inhaled anticholinergic drugs or Aminophylline IV. If ineffective - artificial lung ventilation.

Management of asthmatic status

Prognosis
In case of early detection and adequate treatment the prognosis for the disease is favourable. It becomes serious in severe persistent and poorly controlled (insensitive for corticosteroids) asthma.

The examination of working capacity

The patients with unfavorable for the disease conditions of work need the job replacement. Physical labours with severe asthma are disable to work.

Prophylaxis
Preservation of the environment, healthy life-style (smoking cessation, physical training) are the basis of primary asthma prophylaxis. These measures in combination with adequate drug therapy are effective for secondary prophylaxis.