pathology perspective

1. ASTHMA
COPD

2. DEFINITION
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.

3. HISTORY
• Asthma derived from the Greek word aazein, meaning
“sharp breath”.
• 450 BC, Hippocrates: More likely to occur in tailors,
anglers and metalworkers.
• 250 AD, Galen: Caused by complete or partial bronchial
obstruction.
• 17th century, Bernardino Ramazzini: connection
between asthma and organic dust
• 1901- Use of bronchodilators
• 1960s- Anti Inflammatory medications added to
regimens.

4. BURDEN OF ASTHMA
• Asthma is one of the most chronic disorders
worldwide. Almost 300 million people suffer
from it.
• The overall prevalence of asthma in India is
respectively 2.05% (adults aged ≥15 years)
and 3.49% (adults aged ≥35 years).

7. AMY VAN DYKEN
Olympic champion, former
world record-holder

8. • Asthma may be categorized as atopic
(evidence of allergen sensitization and
immune activation, often in a patient with
allergic rhinitis or eczema) or non-atopic (no
evidence of allergen sensitization). In either
type, episodes of bronchospasm can have
diverse triggers, such as respiratory infections
(especially viral infections), exposure to
irritants (e.g., smoke, fumes), cold air, stress,
and exercise.

9. ATOPIC ASTHMA
• Classic example of IgE-mediated (type I)
hypersensitivity reaction.
• Usually begins in childhood.
• Triggered by allergens like dust, pollen, food
etc,.
• Positive family history.
• High serum IgE levels.

11. NON-ATOPIC
• No evidence of allergen sensitization.
• Usually no family history.
• Respiratory infections due to viruses (e.g.,
rhinovirus, para-influenza virus and
respiratory syncytial virus), smoking, anxiety
and stress are common triggers.

12. Drug induced Asthma
• Pharmacological agents like NSAIDS, β-
blockers, ACE inhibitors.
Aspirin induced asthma is usually
accompanied by urticaria. It is caused by
decrease in PGE2 which inhibits synthesis of pro-
inflammatory mediators such as leukotrienes B4,
C4, D4 and E4.

13. • Occupational asthma : The underlying
mechanisms vary according to stimulus and
include type I reactions, direct liberation of
bronchoconstrictor substances, and
hypersensitivity responses of unknown origin.
• Exercise Induced Asthma: Exercised-induced
asthma is a narrowing of the airways in the
lungs that is triggered by strenuous exercise. It
causes shortness of breath, wheezing,
coughing and other symptoms during or after
exercise.

14. PATHOGENESIS
• Atopic asthma is caused by a TH2 and IgE
response to environmental allergens in
genetically predisposed individuals.
• Release of potent inflammatory mediators and
bronchial wall remodeling are central to it’s
pathophysiology.
• Mucus gland hypertrophy, smooth muscle
proliferation, angiogenesis, fibrosis and nerve
proliferation is witnessed.

16. Immune response
• TH2 Responses, IgE and Inflammation :
A fundamental abnormality in asthma is an
exaggerated TH2 response to normally
harmless environmental antigens.
• IL-4 : stimulates the production of IgE
• IL-5: activates locally recruited eosinophils.
• IL-13: stimulates mucus secretion from
bronchial sub mucosal glands and also
promotes IgE production by B cells.

17. • Inflammatory mediators trigger early-phase and
late phase reactions.
• Early-phase: bronchoconstriction, increased
mucus production, variable degrees of
vasodilation. Bronchoconstriction is triggered by
direct stimulation of subepithelial vagal
(parasympathetic) receptors through both central
and local reflexes triggered by mediators.
• Late-phase: Recruitment of leukocytes, notably
eosinophils, neutrophils, and more T cells.

18. • Mediators whose role in bronchial asthma is
proven beyond doubt:
Leukotrienes C4, D4, and E4, Acetylcholine.
• Others mediators like histamine, platlet-
activating factor, Prostaglndin D2,
neuropeptides, nitric oxide, bradykinin, and
endothelins also contribute to
bronchoconstriction and inflammatory
changes.

21. Genetic factors
• Susceptibility to atopic asthma is multigenic and often
associated with increased incidence of other allergic
disorders, such as allergic rhinitis (hay fever) and
eczema.
• Chromosome 5q: gene cluster encoding IL-3, IL-4, IL-5,
IL-9, and IL-13 and the IL-4 receptor.
• Particular class II HLA alleles are linked to production of
IgE antibodies.
• Polymorphisms in the gene encoding ADAM33, a
metalloproteinase, may be linked to increased
proliferation of bronchial smooth muscle cells and
fibroblasts.
• β receptor gene variants, IL-4 receptor gene variants

22. Environmental factors
• Industrialized cities: airborne pollutants that
serve as allergens.
• Hygiene hypothesis.
• Young children with aeroallergen sensitization
who develop lower respiratory tract viral
infections (rhinovirus type C, respiratory
syncytial virus) have a 10- to 30-fold increased
risk of developing persistent and/or severe
asthma.

23. Clinical features
• Chest tightness, dyspnea, wheezing, and
coughing (with or without sputum production)
are present at a low level constantly.
• Status Asthmaticus: More severe form of
asthma. paroxysm persists for days and even
weeks, sometimes causing airflow obstruction
that is so extreme that marked cyanosis or
even death ensues.

24. Diagnosis
Demonstration of airflow obstruction:
• Prolonged expiration, wheeze.
• Decrease in peak expiratory flow rates.
Blood: Peripheral eosinophilia.
Sputum: Curschmann spirals, and Charcot-
Leyden crystals in the sputum (particularly in
patients with atopic asthma).

25. Plugging of the airways in fatal asthma. Gross view of a sliced
lung specimen to show plugging of the airways in fatal asthma.

26. ASTHMA, MUCUS PLUGS

28. A characteristic finding in sputum or bronchoalveolar
lavage specimens is Curschmann spirals, which may
result from extrusion of mucus plugs from subepithelial
mucous gland ducts or bronchioles.