Asthma

Dr. Naima Tariq

Assistant Professor
 BRONCHIAL ASTHMA
 Asthma is a chronic disorder of the conducting
airways, usually caused by an immunological
reaction, which is marked by episodic
bronchoconstriction due to increased airway
sensitivity to a variety of stimuli; inflammation of
the bronchial walls; and increased mucus
secretion.

• Hyper-reactive airways
– Episodic, reversible bronchconstriction
 Bronchial Asthma
 Clinically it is manifested by
 Wheezing
 Breathlessness
 Chest tightness
 Nighttime or early morning coughing

 Episodes are usually associated with widespread, but

variable, airflow obstruction within the lung that is
often reversible either spontaneously or with
treatment.

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 Bronchial Asthma

• Extrinsic / Atopic / Allergic

– Allergy to exogenous substances

• Intrinsic / Non-atopic

– No exogenous factors identified

Pathogenesis of Asthma
 Pathogenesis
• Type I HSR with exposure to extrinsic allergens
• Initial sensitization to an inhaled allergen
• Stimulate induction of subset 2 helper T cells (CD4 TH2)
that release interleukin (IL)-4 and IL-5
• IL-4 stimulates isotype switching to IgE production.
• IL-5 stimulates production and activation of eosinophils.
• Inhaled antigens cross-link IgE antibodies on mast cells on
mucosal surfaces.
• Release of histamine that stimulate bronchoconstriction,
mucus production, influx of leukocytes
 Pathogenesis contd.
• Late phase reaction (4–8 hours later)
(a) Eotaxin is produced.
Chemotactic for eosinophils and activates eosinophils
(b) Eosinophils release major basic protein (MBP) and
cationic protein that damage epithelial cells and produce
airway constriction
• Other mediators involved
Leukotrienes LTC4-D4-E4 causes prolonged
bronchoconstriction.
Acetylcholine causes airway muscle contraction.
 Genetic Susceptibility.
• It is multigenic and often associated with
increased incidence of other allergic disorders,
such as allergic rhinitis (hay fever) and eczema.

• locus for asthma is located on chromosome 5q,

near the gene cluster encoding the cytokines IL-3,
IL-4, IL-5, IL-9, and IL-13 and the IL-4 receptor.

• Polymorphisms in the gene encoding ADAM33.

 Histopathological changes
• In BRONCHI
(1) Thickening of the
basement membrane
(2) Edema and a mixed
inflammatory infiltrate
(3) Hypertrophy of
submucosal glands
(4)
Hypertrophy/hyperplasia
of smooth muscle cells
 Histopathlogic changes in the
bronchioles
(1) Formation of spiral-shaped mucus plugs
(a) Contain shed epithelial cells called Curschmann spirals
(b) Pathologic effect of MBP and cationic protein

(2) Crystalline granules (galectin 10) in eosinophils coalesce to

form Charcot-Leyden crystals.

(3) Patchy loss of epithelial cells, goblet cell metaplasia

(4) Thick basement membrane

(5) Smooth muscle cell hypertrophy and hyperplasia

 Clinical Manifestations
Symptoms:
 Intermittent dry cough
 Expiratory wheezing
 Shortness of breath
 Chest tightness
 Chest pain
 Fatigue
 Difficulty keeping up with
peers in physical activities
Signs:
 Expiratory wheezing
 Prolonged expiratory phase
 Decreased breath sounds
 Crackles/ rales
 Nasal flaring
 Absence of wheezing in
severe cases
 Laboratory Findings:
 Spirometery showing Airflow Limitation:
Low FEV1
FEV1/ FVC ratio < 0.80

 Bronchodilator response to β-agonist:

Improvement in FEV1 ≥ 12%

 Exercise challenge:
Worsening of FEV1 ≥ 15%

 Daily peak flow or FEV1 AM-PM variation ≥ 20%

 Eosinophilia, positive skin tests for allergens