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
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 shotness of breath 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 inspiratory
wheezing can be heard.
o
Diminished breath sounds
and chest hyperinflation may be observed during acute exacerbations.
o
The presence of
inspiratory 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 unbearableness 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 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 danders,
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.
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
|
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.Exacerbations 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. Exacerbations 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 exacerbations
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.
·
Maintain pulmonary
function as close to normal levels as possible
There
are the followings levels of control: complete, partial, uncontrolled
Complete 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
(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.
|
Drugs
|
Dose on inhalation
|
|
Beklometazon (Beklofort, Beklazon)
|
200-500 mcg
|
|
Budesonid (Budekort)
|
200-400 mcg
|
|
Flutikazon (Fliksotid)
|
100-250 mcg
|
|
Mometazon (Asmaneks)
|
200-400 mcg
|
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
|
|
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 propertie.
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 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 symptoms.
The reliever
medication is a short-acting beta-agonist as needed for symptoms
|
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 needed for symptoms
|
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.
|
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.
