BRONCHIAL ASTHMA

Asthma is defined as a chronic inflammatory disease of airways that is

characterized by increased responsiveness of the tracheobronchial tree to a

multiplicity of stimuli, in which many cells and cellular elements play a role.

This inflammation causes recurrent episodes of wheezing, breathlessness,

chest tightness and coughing, particularly at night or in the early morning.

These episodes are usually associated with widespread but variable airflow

obstruction that is often reversible either spontaneously or with treatment.

Some of the principal cells identified in airway inflammation include mast cells,

eosinophils, epithelial cells, macrophages, and activated T lymphocytes. The

mechanism of inflammation in asthma may be acute, subacute, or chronic, and the

presence of airway edema and mucus secretion also contributes to airflow

obstruction and bronchial reactivity. Varying degrees of mononuclear cell and

eosinophil infiltration, mucus hypersecretion, desquamation of the epithelium,

smooth muscle hyperplasia, and airway remodeling are present.

ETIOLOGY

Genetic factors are of major importance in determining a predisposition to the

development of asthma.

The stimuli that incite acute episodes of asthma can be grouped into seven major

categories:

allergenic,

pharmacologic,

environmental,

occupational,

infectious,

exercise-related, and

emotional

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PATHOGENESIS

Allergic asthma is dependent on an IgE response controlled by T and B

lymphocytes and activated by the interaction of antigen with mast cell–bound

IgE molecules. After taking up an immunogen, these cells migrate to the local

lymph nodes where they present the material to T cell receptors. This leads to

the differentiation of the cell to a TH2 subset and also causes B lymphocytes to

switch their antibody production from IgG and IgM to IgE. Once synthesized

and released by B cells, IgE circulates in the blood until it attaches to high-

affinity receptors on mast cells and low-affinity receptors on basophils.

Immune mechanisms appear to be causally related to the development of

asthma in 25 to 35% of all cases. The pathophysiologic hallmark of asthma is a

reduction in airway diameter brought about by contraction of smooth muscle,

vascular congestion, edema of the bronchial wall, and thick, tenacious

secretions. All these can cause to airway remodeling, which is associated with

structural changes due to long-standing inflammation and may profoundly

affect the extent of reversibility of airway obstruction. BA begins to look like

COPD.

IgE-dependent activation of mast cells leads to release from them big

amount of products of arachidonic acid metabolism. These bioactive substances are

not all the time in cells like histamine or serotonin, and appear during cells

activation and then secreted in extracellular fluid. Free arachidonic acid is used in

two metabolic ways: with the help of cyclooxygenase it changes into

prostoglandings , and with the help of lipooxygenase into the leukotrienes.

Formation of different forms of prostoglandings depends on kind of cells where all

these processes happen. One of forms of prostoglandings PgD2 producing a

bronchoobstructive action much more strong then histamine does.

The typical aspirin-sensitive asthma is most studied. Aspirin inhibits

prostaglandin G/H synthase 1 (cyclooxygenase type 1).

CLINICAL FEATURES

A basic clinical sign of bronchial asthma is an attack of shortness of breath

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because of convertible bronchial obstruction of bronchial tubes due to contraction

of smooth muscle, edema of mucous membrane of bronchial tubes and

hypersecretion of mucus. The net result is an increase in airway resistance, a

decrease in forced expiratory volumes and flow rates, hyperinflation of the lungs

and thorax, increased work of breathing, alterations in respiratory muscle function,

changes in elastic recoil, abnormal distribution of both ventilation and pulmonary

blood flow. During chest examination we can find:

o End-expiratory wheezing or a prolonged expiratory phase is found

most commonly, although inspiration wheezing can be heard.

o Diminished breath sounds and chest hyperinflation may be observed

during acute exacerbation.

o The presence of inspiration wheezing or stridor may prompt an

evaluation for an upper airway obstruction such as vocal cord

dysfunction.

Displays of symptoms increase at night or in an early morning.

Symptoms can increase at the physical loadings, viral infections, influence of

allergens, smoking, change of external temperature condition, strong emotions,

action of chemical aerosols, reception of some medications. Sinusitis, rhinitis,

nasal polyposis are preceded aspirin-sensitive asthma. Combination of clinical

picture of shortness of breath with unbearable of aspirin and nasal polyposis is

named by aspirin or asthmatic triad.

DIAGNOSTICS

Diagnosis is based on the presence of special symptoms which characterized

by day's and seasonal variability. Thick, stringy mucus, which often takes the form

of casts of the distal airways (Curschmann's spirals), when examined

microscopically, often shows eosinophils and Charcot-Leyden crystals. The total

white blood cell count may be slightly increased during an acute attack, and

eosinophilia is common. Pulmonary function tests reveal abnormalities typical

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of obstractive dysfunction, and partial reversibility (improvement FVC or FEV1

of at least 12% or improvement in FEF 25-75 of at least 25%) is often

demonstrated after an inhaled bronchodilator is administered.

An allergist inspection includes:

- collection of allergist anamnesis (presence at patient of eczema,

seasonal or whole-year allergic rhinits, food or medicinal allergy,

and also BA and atopic diseases of his family members). U should

ask about respiratory diseases, age of sick in the moment of

beginning disease, seasonality, improvement of the state of house or

at work, concomitant diseases).

- Total serum immunoglobulin E levels greater than 100 IU are

frequently observed in patients experiencing allergic reactions, but

this finding is not specific for asthma and may be observed in

patients with other conditions (eg, allergic bronchopulmonary

aspergillosis, Churg-Strauss syndrome).

- Allergy skin testing is a useful adjunct in individuals with atopy.

The allergens that most commonly cause asthma are aeroallergens

such as house dust mites, animal dander, pollens, and mold spores.

Two methods are available to test for allergic sensitivity to specific

allergens in the environment: allergy skin tests and blood

radioallergosorbent tests (RAST). Allergy immunotherapy may be

beneficial in controlling allergic rhinitis and asthma symptoms for

some patients.

- Methacholine- or histamine-challenge testing

o Bronchoprovocation testing with either methacholine or histamine

is useful when spirometry findings are normal or near normal,

especially in patients with intermittent or exercise-induced symptoms.

Bronchoprovocation testing helps determine if hyperreactive airways

are present, and a negative test result usually excludes the diagnosis of

asthma.

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Differential diagnosis

The differentiation of asthma from other diseases associated with dyspnea

and wheezing is usually not difficult, particularly if the patient is seen during an

acute episode. A personal or family history of allergic diseases such as eczema,

rhinitis, or urticaria is valuable contributory evidence.

Recurrent episodes of bronchospasm can occur with carcinoid tumors ,

recurrent pulmonary emboli , and chronic bronchitis. In chronic bronchitis there

are no true symptom-free periods, and one can usually obtain a history of chronic

cough and sputum production as a background on which acute attacks of wheezing

are superimposed.

Eosinophilic pneumonias are often associated with asthmatic symptoms, as

are various chemical pneumonias and exposures to insecticides and cholinergic

drugs. Bronchospasm is occasionally a manifestation of systemic vasculitis with

pulmonary involvement.Differential diagnostics of COPD and BA

Sign COPD BA

Allergy Not characteristic characteristic

Cough Periodic or permanent paroxysmal

Shortness of breath Permanent Attacks of expiration

shortness of breath

Daily allowance changes

of FEV1

Less than, than 10% from

normal

More than 12% from

normal

Bronchial obstruction Making progress decline

of function of lungs

There is not a making

progress decline of

function of lungs,

convertibility is

characteristic

Eosinophilia of blood and

sputum

Not characteristic Characteristic

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CLINICAL CLASSIFICATION

Intermittent asthma:

1. Intermittent symptoms occurring less than once a week

2. Brief exacerbations

3. Nocturnal symptoms occurring less than twice a month/

4. Asymptomatic with normal lung function between exacerbations.

5. FEV1 or PEF rate greater than 80%, with less than 20% variability

Mild persistent

1.Symptoms occurring more than once a week but less than once a day

2.Exacerbation affect activity and sleep

3. Nocturnal symptoms occurring more than twice a month

4. FEV1 or PEF rate greater than 80% predicted, with variability of 20-30%

Moderate persistent

1. Daily symptoms

2. Exacerbation affect activity and sleep

3. Nocturnal symptoms occurring more than once a week

4. FEV1 or PEF rate 60-80% of predicted, with variability greater than 30%

Severe persistent

1.Continuous symptoms

2.Frequent exacerbation

3.Frequent nocturnal asthma symptoms

4.Physical activities limited by asthma symptoms

5.FEV1 or PEF rate less than 60%, with variability greater than 30%

TREATMENT

The goals for successful management of asthma include the following:

Achieve and maintain control of symptoms.

Prevent asthma exacerbations.

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Maintain pulmonary function as close to normal levels as possible

There are the followings levels of control: complete, partial, uncontrolledComplete control

Description Control flow

Daily symptoms not

Limitation of activity not

Nightly symptoms not

Using of в2-agonists for a removal

attacks of shortness of breath

not

FVD normal indexes

acute condition not

Drug therapy of BA:

– the different ways of introduction of drugs are used:

- inhalation

- peroral

- parenterally.

Preparations for treatment BA used protractedly for maintenance of BA

control.

Most preferable way – inhalation. For rapid relief of symptoms short-acting

beta-agonists are used . Sometimes more expressed positive answer is observed

from short-acting cholinergic antagonist.

Drugs Dose (mcg) Duration of

action

short-acting beta-agonists:

salbutamol (Ventolinum),

Fenoterol (Berotek).

100

100

4-6

4-6

short-acting cholinergic antagonist:

Ipratropiya bromide (Ipravent) 20, 40 6-8

Combined drugs

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(short-acting beta-agonists +

short-acting cholinergic antagonist:

Fenoterol + Ipratropiya bromide (berodual)

salbutamol + Ipratropiya bromide ()

Inhaled Glucocorticoids

These drugs are indicated in patients with persistent symptoms. These drugs share

the ability to control inflammation, facilitate the long-term prevention of

symptoms, reduce the need for oral glucocorticoids, minimize acute occurrences,

and prevent hospitalisations.

The most high type of safety and low system biotavailability is marked at

Flutikazon and Mometazon.

Cromolyn sodium and nedocromil sodium-their major therapeutic effect is to

inhibit the degranulation of mast cells, thereby preventing the release of the

chemical mediators of anaphylaxis.

Long-acting inhaled β2-agonists should not be used for symptom relief or

for exacerbations. Use only with inhaled glucocorticoids.

Long-acting inhaled β2-agonists

Drugs Dose (mcg) Duration of

action

Long-acting inhaled β2-agonists

Salmeterol (Serevent)

Formoterol (Zafiron)

25, 50

4, 12

12

12

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Drugs Dose on inhalation

Beklometazon (Beklofort, Beklazon) 200-500 mcg

Budesonid (Budekort) 200-400 mcg

Flutikazon (Fliksotid) 100-250 mcg

Long-acting cholinergic antagonist

Tiotropiya bromide (Spiriva) 18 24

Combination beta-agonist/corticosteroid

Inhaled combination medication used frequently in the treatment of asthma

consists of a long-acting beta-agonist and inhaled corticosteroid .

SERETID (salmeterol +fluticasone) has dosages 50/25, 125/25, 250/25.

Simbikort (Budesonid + Formoterol) – 200/ 4

There are different deliverable devices – evohaler, дискус, твист-халер,

турбухалер, easy breathing. It is better to appoint the high doses of inhalation

steroids through spacer (demonstration). Modern deliverable device is

NEBULAYZER (nebula means fog). With their help it is possible to inhale long

and short acting beta-agonists, inhaled glucocorticoids.

Glucocorticoids are the most potent and most effective anti-inflammatory

medications available. Systemic steroids are most beneficial in acute illness, when

severe airway obstruction is not resolving, and in chronic disease, when there has

been failure of a previously optimal regimen with frequent recurrences of

symptoms of increasing severity. A preference gives to prednisolone (5 mg=1 tab.)

or to Methylprednisolone (4 mg = 1 tab.)

METHYLXANTHINES

Theophylline and its various salts are medium-potency bronchodilators with

questionable anti-inflammatory properties.

For maintenance therapy, long-acting theophylline compounds are available and

are usually given once or twice daily. Single-dose administration in the evening

reduces nocturnal symptoms and helps keep the patient complaint-free during the

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day. They are now considered second-line therapy, and as such they are rarely used

in acute situations and infrequently in chronic ones.

For basic - the long-term control of asthma inhaled glucocorticoids, inhaled

glucocorticoids with long-acting beta-agonists, long-acting cholinergic antagonist,

systemic steroids, long-acting theophylline, combined short-acting beta-agonists

are used. step approach in treatment of bronchial asthma

Intermittent

asthma

Mild persistent Moderate persistent Severe persistent

A controller

medication is not

needed.

The reliever

medication is a

short-acting beta-

agonist as needed

for symptoms

The controller

medication is an

inhaled

corticosteroid

(200-500 mcg),

cromolyn (adult:

2-4 puffs tid/qid;

child: 1-2 puffs

tid/qid),

nedocromil, or a

leukotriene

antagonist. If

needed, increase

the dose of

corticosteroid and

add a long-acting

beta-agonist or

sustained-release

theophylline,

especially for

nocturnal

The controller

medication is an

inhaled corticosteroid

(800-2000 mcg) and a

long-acting

bronchodilator (either

beta-agonist or

sustained-release

theophylline) A

combination

medication of

salmeteorol/fluticasone

(Advair) is a preferred

choice to improve

compliance. Other

agents may include

leukotriene modifying

agents or omalizumab.

The reliever

medication is a short-

acting beta-agonist as

The controller

medication is an

inhaled

corticosteroid

(800-2000 mcg), a

long-acting

bronchodilator

(beta-agonist

and/or

theophylline), and

long-term oral

corticosteroid

therapy.

The reliever

medication is a

short-acting beta-

agonist as needed

for symptoms.

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symptoms.

The reliever

medication is a

short-acting beta-

agonist as needed

for symptoms

needed for symptoms

Mucolytic agents are used in symptomatic therapy (group of bromhexine,

ambroxole (lasolvan).

Information on the clinical course of asthma suggests a good prognosis,

particularly for those whose disease is mild and develops in childhood.

Prophylaxis

Primary – individual and social conditions, directed on avoidance of

disease- healthy way of life, improvement of house conditions, effective treatment

of rhinosinusitis, chronic infection.

Second – full and in time treatment of exacerbations, selection of adequate

base therapy, treatment of concomitant diseases.

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