ASTHMA
► Asthma is defined as a chronic inflammatory disorder of airways
which is associated with airway hyper-responsiveness.
► Chronic inflammation is associated with airway hyper
responsiveness that leads to recurrent episodes of wheezing,
breathlessness, chest tightness and coughing, particularly At
night and in the early morning ·
► These are usually associated with widespread but variable
airflow obstruction within the lungs that is often reversible
either spontaneously or with treatment.
► Though symptoms and bronchospasm are intermittent, airway
inflammation is persistent. l
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Based on the concept of persistent airway inflammation, two
important principles have emerged. a
First, the disease is chronic, often life-long; second, its severi ty
fluctuates and sometimes there may be prolonged remissions.
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► Asthma was earlier divided into two types.... I
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► 1. Intrinsic or non atopic or non allergic II
► 2. Extrinsic or atopic or allergic I
► But nowadays asthma is not differentiated into either of thetw
categories
AETIOPATHOGENESIS
► Aetiological factors are divided into 2 groups...
► 1. Risk factors
► 2. Trigger factors
RISK AEiTORS AND iTRIGGERS
RISK FACTORS
ENDOGENOUS FACTORS ENVIRONMENTAL FACTORS
Genetic predisposition Indoor allergens
Atopy Outdoor allergens
Airway hyperresponsiveness Occupational sensitizers
Gender Passive smoking
Ethnicity Respiratory infections
Diet
TRIGERRS
" .
. - Drugs (B blockers, aspirin)
Upper respiratory tract viral infections Stress
Exercise and hyperventilation Sulfur dioxide and irritant gases
Irritants (household sprays, paint fumes)
RISK FACTORS
GENETIC PREDISPOSITION
► Polymorphism of gene on chromosome 5 q --- linked to the
synthesis of lgE , a gene at 11 q --- atopy
ATOPY
► Patient with asthma commonly suffers from other atopic
diseases like allergic rhinitis , atopic dermatitis ...
GENDER
► Ratio is equal in both sex in adults
ETHNICITY
► Affects globally, but prevalence is increased with increased
urbanization
OBESITY
► BMI > 30
ALLERGENS
► Inhaled allergens --- dermatophagoides (house dust mite) ,
allergens from pets, cat , cockroach, grass pollen ...
OCCUPATIONAL SENSITIZERS
► Exposure to chemicals
INFECTIONS
► Respiratory viral and bacterial infections
DIET
► Diet low in antioxidants such as vitamin C, vitamin A,
magnesium, selenium, omega 3 pufa or diet high in sodium ,
omega 6 pufa ·
FOOD ALLERGENS
PATHOGENESIS
Initial Sensitisation
► T-lymphocytes play a key role in asthmatic airway inflamrT1ation
and sensitisation.
► There are two types of T-lymphocyte helper (Th) cells . Th1
controls synthesis of lgs such as lgA and lgM whereas Th 2
controls lgE production.
► Usually, there is a balance between Th1 /Th 2 switch .
► Exposure to an inducing factor sensitizes T cells of a person
with genetic susceptibility with bronchial asthma, and it shifts
the Th1 /Th 2 switch in favour of Th 2 dominance.
► Once sensitized, these Th 2 cells get into airway mucosa and
governs lgE mediated responses of allergic reaction. \
► In a normal individual, when a noxious allergic substance enters
the airway, lgA is released. However, in a sensitized person ·igE
is released.
PATHOLOGY
► The airway mucosa is infiltrated with activated eosinophils and li
lymphocytes (mostly Th2) , and there is activation of mucosal mast
cells.
► There are structural changes in the airways (described as
remodeling)
►A characteristic finding is thickening of the basement
membrane due to subepithelial collagen deposition.
► The epithelium is often shed or friable, with reduced
attachments to the airway wall and increased numbers of
epithelial cells in the lumen.
► The airway wall may be thickened and edematous in severe
asthma.
► Occlusion of the airway lumen by a mucous plug , which is
comprised of mucous glycoproteins secreted from goblet cells .
► There is also vasodilation and increased numbers of blood ·
vessels (angiogenesis).
► Direct observation by bronchoscopy shows that the airways ar
narrowed , erythematous , and edematous.
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AIRWAY INFLAN1MAJION I
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It is induced by inflammatory cells like, II
► MAST CELLS I
► MACROPHAGES AND DENDRITIC CELLS
► EOSINOPHILS
► NEUTROPHILS
► T LYMPHOCYTES
► There is inflammation in the respiratory mucosa from the
trachea to terminal bronchioles , but with a predominance in
the bronchi (cartilaginous airways)
► The specific pattern of airway inflammation in asthma is
associated with airway hyper responsiveness (AHR) .
EFFECTS OF INFLA,vvv1AJION
AIRWAY EPITHELIUM
► Airway epithelial shedding may be contributing to AHR
► Epithelial damage may contribute to AHR by --- loss of itsl
barrier function to allow penetration of allergens , loss ot'&
enzymes (such as neutral endopeptidase) that degrade certain
peptide inflammatory mediators
FIBROSIS
► In all asthmatic patients, the basement membrane is apparently
thickened due to subepithelial fibrosis with deposition of types
Ill and V and is associated with eosinophil infiltration .
VASCULAR RESPONSES
► There is an increase in the number of blood vessels in ast~ ti
airways as a result of angiogenesis in response to growth factor ,
particularly vascular endothelial growth factor.
MUCUS HYPERSECRETION
► Increased mucus secretion contributes to the viscid mucous
plugs that occlude asthmatic airways, particularly in fatal
asthma.
► IL-13 induces mucus hypersecretion.
AIRWAY REMODELING
► Several changes in the structure of the airway are
characteristically found in asthma, and these may lead to
irreversible narrowing of the airways.
AIRWAY HYPERRESPONSIVENESS
► AHR is the characteristic physiologic abnormality of asthma and
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.
CLINICAL FEATURES
► The characteristic symptoms of asthma are wheezing , dyspnea,
chest tightness and coughing, which are variable, both
spontaneously and with therapy.
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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 , witli
typically tenacious mucus that is difficult to expectorate.
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► Prodromal symptoms may precede an attack, with itching under.
the chin , discomfort between the scapulae, or inexplicable fea ~
(impending doom).
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Typical physical signs are inspiratory, and to a greater extent
expiratory, rhonchi throughout the chest, and there may oe
hyperinflation.
► Some patients, particularly children, may present with a
predominant nonproductive cough (cough-variant asthma) .
► During severe exacerbation of asthma wheezing may be absent
due to severely reduced airflow, but exacerbation can be
identified by the presence of other signs , such as hyper
ventilation (increased respiratory rate), flaring of alae nasi , use
of accessory muscles of respiration and pulsus paradoxus.
DIAGNOSIS
LUNG FUNCTION TESTS
► Simple spirometry confirms airflow limitation with a reduced
FEV1, FEV1 / FVC ratio , and PEF.
► Reversibility is demonstrated by a >12% and 200-ml increase in
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FEV1 15 min after an inhaled short-acting B2-agonist or in som
patients by a 2- to 4-week trial of oral corticosteroids (OCS)
(prednisone or prednisolone 30-40 mg daily).