2. Asthma
Is a heterogeneous disease, usually characterized by
chronic airway inflammation, is defined by the
history of respiratory symptoms such as wheeze,
shortness of breath, chest tightness and cough that
vary over time and in intensity, together with variable
expiratory airflow limitation.
3. Bronchial asthma (BA) is a chronic recurrent
inflammatory process in the airways, characterized by
bronchial hyperreactivity and clinically manifested by
recurrent symptoms of wheezing, asthma, cough due
to bronchospasm, hypersecretion and edema of the
bronchial mucosa.
The hyperreactivity of the bronchi - their increased
sensitivity to various stimuli. Bronchial hyperreactivity
is the main pathophysiological sign of asthma, which
underlies airway instability.
4. Epidemiology
Between 100 and 150 million people around the globe
suffer from asthma and this number is rising.
World-wide, deaths from this condition have reached
over 180,000 annually.
5. Etiology
Asthma is a heterogeneous disease with interplay
between genetic and environmental factors.
Allergic asthma
Non-allergic asthma
6. Etiological factors of asthma are
divided into internal and external.
Internal factors are genetic defects that contribute to
the development of asthma;
External factors are factors that directly provoke the
disease.
External factors are divided into:
- inducers - cause inflammation and hypersensitivity of
the respiratory tract;
- Triggers (stimulants) - lead to bronchospasm.
7. Inductors:
- allergens (atopic): food, drug, fungal, house dust, plant
pollen, allergens of animals, insects, mites;
- mechanical and chemical irritants: acid vapors, alkalis,
detergents, varnishes, paints, solvents, salts of heavy metals
(chromium, nickel, platinum);
- viral, bacterial infections.
Triggers:
- hypothermia (inhalation of cold air);
- physical activity;
- emotional stress;
- change in temperature, atmospheric pressure, humidity.
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12. In case of BA airways will be
narrowed, erythematous,
and edematous.
13. The specific pattern of airway
inflammation in asthma is
associated with airway
hyperresponsiveness (AHR), the
physiologic abnormality of
asthma, which is correlated with
variable airflow obstruction.
14. Pathogenesis
In the pathogenesis of asthma, generalized allergic
inflammation, which develops in the bronchial wall
under the influence of immune and non-immune
reactions, is of major importance.
The most important is type I allergic reaction (atopic),
which consists of 3 stages.
15. І stage- immunological
When a specific allergen enters a sensitized body, a large
amount of IgE is produced, which is fixed on the mast cell and,
by binding to the antigen, leads to the activation of the mast
cell.
ІІ stage - pathochemical
Due to the activation of the mast cell, biologically active
substances (BAS) are released: histamine, serotonin,
leukotrienes (especially C4D4), prostaglandins, platelet
activating factor and others). This leads to allergic bronchitis.
ІІІ stage - pathophysiological
Under the influence of BAS increases the permeability of the
microcirculatory tract → develops mucosal edema, there is
bronchospasm, hypersecretion, syndrome of disseminated
intravascular coagulation (DIC syndrome).
All this leads to acute bronchial obstruction, so the attack of
asthma develops.
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19. Mast cells are important in initiating the acute
bronchoconstrictor responses to allergens and several
other indirectly acting stimuli such as exercise and
hyperventilation (via osmolality or thermal changes), as
well as fog.
Activated mast cells are found at the airway surface in
asthma patients and also in the airway smooth-muscle
layer, whereas this is not seen in normal subjects
• Mast cells are activated by allergens through an IgE-
dependent mechanism, and binding of specific IgE to
mast cells renders them more sensitive to activation.
• Mast cells release several bronchoconstrictor mediators,
including histamine, prostaglandin D 2 , and cysteinyl-
leukotrienes, but also several cytokines, chemokines,
growth factors, and neurotrophins.
20. Macrophages and dendritic cells
may traffic into the airways in asthma and may be activated by
allergens via low-affinity IgE receptors (Fc ε RII).
Macrophages have the capacity to initiate a type of inflammatory
response via the release of a certain pattern of cytokines but these
cells also release anti-inflammatory mediators (e.g., IL-10)
Dendritic cells are specialized macrophage-like cells in the airway
epithelium, which are the major antigen-presenting cells.
Dendritic cells take up allergens, process them to peptides, and
migrate to local lymph nodes where they present the allergenic
peptides to uncommitted T-lymphocytes to program the production
of allergen-specific T cells.
Immature dendritic cells in the respiratory tract promote Th2 cell
differentiation and require cytokines such as IL-12 and tumor necrosis
factor α (TNF-α), to promote the normally preponderant Th1
response.
The cytokine thymic stromal lymphopoietin (TSLP) released from
epithelial cells in asthmatic patients instructs dendritic cells to
release chemokines that attract Th2 cells into the airways.
21. Eosinophils
Allergen inhalation results in a marked increase in
activated eosinophils in the airways at the time of the late
reaction. Eosinophils are linked to the development of AHR
through the release of basic proteins and oxygen-derived
free radicals.
Eosinophil recruitment involves adhesion of eosinophils to
vascular endothelial cells in the airway circulation due to
interaction between adhesion molecules, migration into
the submucosa under the direction of chemokines, and
their subsequent activation and prolonged survival.
Increasing evidence suggests that eosinophils may be
important in release of growth factors involved in airway
remodeling, in exacerbations.
22. T lymphocytes
T lymphocytes play a very important role in coordinating the
inflammatory response in asthma through the release of specific
patterns of cytokines, resulting in the recruitment and survival of
eosinophils and in the maintenance of a mast cell population in the
airways.
The naive immune system and the immune system of asthmatics are
skewed to express the Th2 phenotype, whereas in normal airways Th1
cells predominate. Th2 cells, through the release of IL-5, are associated
with eosinophilic inflammation and, through the release of IL-4 and IL-
13, are associated with increased IgE formation.
Regulatory T cells play an important role in determining the expression
of other T cells, and there is evidence for a reduction in a certain subset
of regulatory T cells (CD4 + CD25 + ) in asthma that is associated with
increased Th2 cells.
23.
24. AIRWAY HYPERRESPONSIVENESS
AHR is the characteristic physiologic abnormality of asthma
describes the excessive bronchoconstrictor response to multiple
inhaled triggers that would have no effect on normal airways.
The increase in AHR is linked to the frequency of asthma
symptoms, and, thus, an important aim of therapy is to reduce
AHR.
Increased bronchoconstrictor responsiveness is seen with direct
bronchoconstrictors such as histamine and methacholine, which
contract airway smooth muscle, but is characteristically also seen
with many indirect stimuli, which release bronchoconstrictors
from mast cells or activate sensory nerves.
Most of the triggers for asthma symptoms appear to act indirectly,
including allergens, exercise, hyperventilation, fog (via mast cell
activation), irritant dusts, and sulfur dioxide (via a cholinergic
reflex).
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26.
27. Classification
1. External asthma (atopic) - a known cause of
asthma.
2. Internal asthma (infectious-dependent) - an
unknown factor that causes asthma attacks.
During:
Aggravation
Fading exacerbation
Remission
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29.
30.
31. CLINICAL FEATURES
The characteristic symptoms of asthma are wheezing, dyspnea, and
coughing, which are variable, both spontaneously and with therapy.
Symptoms may be worse at night and patients typically awake in the early
morning hours.
Patients may report difficulty in filling their lungs with air.
There is increased mucus production in some patients, with typically
tenacious mucus that is difficult to expectorate.
There may be increased ventilation and use of accessory muscles of
ventilation.
Prodromal symptoms may precede an attack, with itching under the chin,
discomfort between the scapulae, or inexplicable fear (impending doom).
Typical physical signs are inspiratory, and to a greater extent expiratory,
rhonchi throughout the chest, and there may be hyperinflation.
Some patients, particularly children, may present with a predominant
nonproductive cough (cough-variant asthma).
There may be no abnormal physical findings when asthma is under control.
32.
33. Diagnosis
The diagnosis of asthma is usually apparent from the
symptoms of variable and intermittent airways
obstruction, but is usually confirmed by objective
measurements of lung function.
34. Lung function tests
Simple spirometry confirms airflow limitation with a
reduced FEV 1 , FEV 1 /FVC ratio, and PEF.
Reversibility is demonstrated by >12% and 200-mL
increase in FEV 1 15 minutes after an inhaled short-acting
β 2 -agonist or in some patients by a 2 to 4 week trial of oral
corticosteroids (OCS) (prednisone or prednisolone
30–40 mg daily).
Measurements of PEF twice daily may confirm the diurnal
variations in airflow obstruction.
whole body plethysmography shows increased airway
resistance and may show increased total lung capacity and
residual volume.
Gas diffusion is usually normal
35.
36. Test with salbutamol: increase FEV1 13%.
Indicants Proper Absolute %
RR, /min 12
TV, l 0,97
PMV, л 12,8
VC, l 3,8 2,99 80,6
IRV, l 1,23
ERV, l 0,71
PRV 0,76 1,14 150
TLC 4,56 4,4 104
FVC, l 3,9 4,4 102
FEV1, l 3,24 2,2 67,9
FEV1/ FVC, % 54,1
FEV 25, l/s 7,02 2,84 44,4
FEV 50, l/s 4,81 2,38 49,5
FEV 75, l/s 2,53 2,0 79,1
Examination of respiratory function № 4
The reduction of FEV1, the Tiffon coefficient, the vital capacity of the lungs (VC) is
normal a violation of pulmonary ventilation of the obstructive type, characteristic
of diseases pathogenetically associated with respiratory tract (bronchial asthma,
COPD, emphysema). According to samples with salbutamol, pulmonary
ventilation is reversible, which allows for the establishment of bronchial asthma.
Indicators OFV1 in the range of 60-80% of the proper characteristic for persistent
bronchial asthma of moderate severity.
37. Examination of respiratory function № 5
Indicants Proper Absolute %
RR, /min 12
TV, l 0,99
PMV, л 11,88
VC, l 3,8 3,7 97,4
IRV, l 1,43
ERV, l 1,22
PRV 0,76 0,89 117,1
TLC 4,56 4,32 74,7
FVC, l 3,9 4,1 105
FEV1, l 3,24 2,75 84,8
FEV1/ FVC, % 67,1
FEV 25, l/s 6,39 2,54 39,7
FEV 50, l/s 4,81 2,40 49,9
FEV 75, l/s 2,53 1,88 74,3
Test with salbutamol: increase FEV1 15%.
The reduction of FEV1, the Tiffon coefficient, the vital capacity of the lungs (VC) is
normal a violation of pulmonary ventilation of the obstructive type, characteristic of
diseases pathogenetically associated with respiratory tract (bronchial asthma, COPD,
emphysema). According to test with salbutamol, pulmonary ventilation is reversible,
which allows for the establishment of bronchial asthma. Indicator FEV1> 80% of the
proper characteristic for both intermittent and light persistent bronchial asthma.
38. Hematologic tests
Blood tests are not usually helpful.
Total serum IgE and specific IgE to inhaled allergens
[radioallergosorbent test (RAST)] may be measured in
some patients.
39. Analysis of sputum or bronchial secretions
(eosinophils, Сurschmann spirals, Charcot-Leyden crystals)
40. Global analysis of the sputum №3
Date of the examination___________________________________________________________
Name of the patient_______________________________________________________________
Macroscopic analysis
Color white
Consistency glassy
Character mucic
Microscopic analysis of the native smear
Alveolar macrophages 1-3 within of eyeshot
Epithelial cells 0-1 within of eyeshot, cylinder
Leucocytes 4-5 within of eyeshot, eosinophiles
Erythrocytes singular within of eyeshot
Curshmann’s spirals +
Charcot-Leyden
crystals
++
Elastic fibers not define
Cholesterol crystals not define
Crystals of hematoidin not define
Atypical cells not define
Microscopic analysis after Gram’s stain
Bacterial flora not define
Conclusion: The mucosal character and the vitreous consistency of sputum,
the presence of leukocytes (eosinophils), alveolar macrophages, the Kurshman
spirals, and Charcot-Leiden's crystals indicate an immune inflammatory
process of non-microbial origin in the respiratory organs that go over with
bronchospasm (after an asthmatic attack in patients with bronchial asthma) .
41. Global analysis of the sputum №5
Date of the examination___________________________________________________________
Name of the patient_______________________________________________________________
Macroscopic analysis
Color white
Consistency Glassy
Character Mucous
Microscopic analysis of the native smear
Alveolar macrophages 1-3 within of eyeshot
Epithelial cells 2-4 within of eyeshot, cylinder
Leucocytes 4-5 within of eyeshot, eosinophils
Erythrocytes 0-1 within of eyeshot
Curshmann’s spirals +
Charcot-Leyden
crystals
+
Elastic fibers not define
Cholesterol crystals not define
Crystals of hematoidin not define
Atypical cells not define
Microscopic analysis after Gram’s stain
Bacterial flora not define
Conclusion: The mucosal nature and vitreous consistency of sputum, the
presence of leukocytes (eosinophils), alveolar macrophages, peptic epithelium,
Kurshman spirals, and Charcot-Leyden crystals indicate an immune
inflammatory process of non-microbial origin in the respiratory organs that go
over with bronchospasm (after an attack of stomachs in patients with bronchial
asthma).
42. Posteroanterior chest radiograph demonstrates a
pneumomediastinum in bronchial asthma. Mediastinal
air is noted adjacent to the anteroposterior window and
airtrapping extends to the neck, especially on the right
side.
Lateral chest radiograph
demonstrates a pneumomediastinum
in bronchial asthma. Air is noted
anterior to the trachea (same patient
as in the previous image).
43. High-resolution CT scan of the thorax obtained
during expiration demonstrates a mosaic pattern of
lung attenuation in a patient with asthma. Lucent
areas (arrows) represent areas of airtrapping (same
patient as in the previous image).
44. High-resolution CT scan of the thorax
obtained during inspiration in a patient
with recurrent left lower lobe pneumonia
shows a bronchial mucoepidermoid
carcinoma (arrow).
Note the normal increase in right lung
attenuation during expiration (right
arrow). The left lung remains lucent,
especially the upper lobe, secondary to
bronchial obstruction with airtrapping
(left upper arrow). The vasculature on
the left is diminutive, secondary to reflex
vasoconstriction. Left pleural thickening
and abnormal linear opacities are noted
in the left lower lobe; these are the result
of prior episodes of postobstructive
pneumonia (left lower arrow).
45. Treatment
Therapeutic measures for asthma should be divided
into:
1. Treatment of asthma attacks;
2. Treatment of allergic inflammation;
In the phase of stable remission, asthma does not
require treatment.
