Asthma

https://www.webmd.com/asthma/ss/slideshow-asthma-overview BIOC3364_2021
 Malfunctions and Diseases of
the Respiratory System
A severe allergic reaction characterized by the constriction
asthma
of bronchioles
(chronic) Inflammation of the lining of the bronchioles, (chronic cough,
bronchitis sputum in the morning)

A condition in which the alveoli deteriorate, causing the lungs

emphysema
to lose their elasticity, trouble exhaling air from the lung

A condition in which the alveoli become filled with fluid,

pneumonia preventing the exchange of gases. Caused by bacteria, viruses
or fungi.

An irregular and uncontrolled growth of tumors in the lung

lung cancer
tissue, in the main part near the air sacs

Genetic disease - thick and sticky mucus that clogs up tubes

cystic fibrosis and passageways. Repeat and dangerous lung infections, as
(CF) well as obstructions in the pancreas that prevent important
enzymes from breaking down nutrients for the body.
Pathology – Respiratory tract
 Malfunctions and Diseases of
the Respiratory System
A severe allergic reaction characterized by the constriction
asthma
of bronchioles
(chronic) Inflammation of the lining of the bronchioles, (chronic cough,
bronchitis sputum in the morning)

A condition in which the alveoli deteriorate, causing the lungs

emphysema
to lose their elasticity, trouble exhaling air from the lung

A condition in which the alveoli become filled with fluid,

pneumonia preventing the exchange of gases. Caused by bacteria, viruses
or fungi.

An irregular and uncontrolled growth of tumors in the lung

lung cancer
tissue, in the main part near the air sacs

Genetic disease - thick and sticky mucus that clogs up tubes

cystic fibrosis and passageways. Repeat and dangerous lung infections, as
(CF) well as obstructions in the pancreas that prevent important
enzymes from breaking down nutrients for the body.
SARS-CoV-2 – host interactions
in the lungs
 Malfunctions and Diseases of
the Respiratory System
A severe (allergic) (inflammatory) reaction characterized by
asthma
the constriction of bronchioles
(chronic) Inflammation of the lining of the bronchioles, (chronic cough,
bronchitis sputum in the morning)

A condition in which the alveoli deteriorate, causing the lungs

emphysema
to lose their elasticity, trouble exhaling air from the lung

A condition in which the alveoli become filled with fluid,

pneumonia preventing the exchange of gases. Caused by bacteria, viruses
or fungi.

An irregular and uncontrolled growth of tumors in the lung

lung cancer
tissue, in the main part near the air sacs

Genetic disease - thick and sticky mucus that clogs up tubes

cystic fibrosis and passageways. Repeat and dangerous lung infections, as
(CF) well as obstructions in the pancreas that prevent important
enzymes from breaking down nutrients for the body.
Asthma (Greek for “laboured breathing”)
 A chronic (long-term) lung disease that inflames and
narrows the airways – making breathing hard

 Characterized by increased responsiveness (hyper

responsiveness) of the airways to various stimuli and
manifested by widespread obstruction, which changes in
severity either spontaneously or as a result of therapy

 Symptoms include: recurring periods of wheezing (a

whistling sound when you breathe), chest tightness,
shortness of breath, and coughing – asthma triad

 The coughing often occurs at night or early in the morning

 The most common chronic disease among children

Closer look at the bronchiole
Normal Asthmatic

 Narrowed airway limiting air flow

 Tightened muscles constrict air flow
- bronchoconstriction
 Inflamed and thickened airways
 Excess mucus clogs the airway
 Asthma disparities

 Rates of hospitalization for asthma for Blacks are

almost triple those for Whites
 Death from asthma is 3 times more likely to occur
among Blacks than Whites
 Among adults, women of all races have higher rates
of illness and death from asthma than men
 Among children, boys are more likely to suffer from
asthma than girls
 Causes
 Exact cause not known

 Variety of factors interacting with one another, early in

life, result in the development of asthma

 Parents with asthma

 Atopy – inherited predisposition to develop IgE

 Childhood respiratory infections (e.g. RSV)

 Exposure to allergens or infections while the immune

system is developing – the “hygiene hypothesis”

 Median age of onset is 4 years with 20% developing

symptoms in first year of life; 60% resolve by adulthood
Common Triggers
 Triggers
 A variety of things can cause asthma symptoms to appear:

 Allergens - seasonal allergens, indoor allergens, pets

 Irritants - cigarette smoke, wood smoke, other

pollutants, weather changes, perfume, cleaning products

 Food and drinks

 Medicines – aspirin, NSAID, beta-blockers etc.

 Physical activity – may exacerbate

 Upper respiratory infections (viral origin - rhinovirus,

influenza, RSV, parainfluenza) and sinus infections
 Types of asthma
 People use many terms to describe the different types
of asthma. Sometimes the terms and categories overlap:

 Allergic asthma
 Non-allergic asthma
 Allergic bronchopulmonary mycosis
 Aspirin-induced asthma
 Adult-onset asthma
 Asthma with fixed airflow obstruction
 Exercise-induced asthma
 Eosinophilic asthma
 Cough-variant asthma
 Work-related asthma
 Nighttime (Nocturnal) asthma
 Asthma with obesity
 Types of Asthma
Extrinsic Intrinsic
Cause Atopy – type I Non-atopic – non-
hypersensitivity immune
(immediate)
Trigger Hypersensitivity to Cold weather,
environmental exercise, aspirin,
antigens – pollen, stress, ozone, second-
pathogens, food hand smoking, air
etc. pollution, upper
respiratory tract
infections (RSV,
parainfluenza)
IgE- Yes No
mediated
Onset Begins in childhood
 Pathology of asthma

Asosingh and Erszurum, (2009) Biochem. Soc. Trans. 37, 805–810; doi:10.1042/BST0370805
Pathophysiology of asthma

Additional information – see the video

 Mast cells
mediator release
 Local immune disbalance
Th2 > Th1

 Production of IgE

 IgE attached to the mast

cells – hyperresponsive

 Cross-linking of FcRI
receptors results in
degranulation

 Sometimes – direct
triggers – opiates,
vancomycin etc.
Aspirin makes asthma worse

Steroids X

X Zileuton

Aspirin X
NSAIDs
B4
C4
D4
E4

https://tmedweb.tulane.edu/pharmwiki/doku.php/introduction_to_eicosanoids
 Human lung blood circulation
 Two blood supply
systems:

 a bronchial vasculature –
the systemic arterial
blood supply providing
oxygenated blood and
nutrients to the lung
tissue

 a pulmonary vasculature
carrying deoxygenated
blood from the right
ventricle to the lungs for
oxygenation (>95%)
 Neovascularization in asthma
 The pathophysiology of asthma is related to allergy, and/or
infections with respiratory viruses

 Inhalational exposures with allergens, or virus infections, trigger

asthma exacerbations

 In the case of an allergen, antigen-presenting cells capture the

allergen and trigger immune responses skewed towards Th2 cells

 Th2 cells induce allergen-specific IgE production by B-cells, which

bind to the surface of mast cells

 Mast cells degranulate upon their subsequent encounter with

allergen(s)

 Mast cell and T-cell derived products induce a cascade reaction

involving structural vascular cells and airway epithelial cells that
result in the recruitment of eosinophils, typical effector cells in
asthma
 Neovascularization in asthma
 Damage to structural lung cells (epithelial cells, endothelial cells and
smooth-muscle cells) is caused by eosinophil-derived products, which
leads to airway hyper-responsiveness and airway remodeling

 VEGF (and other yet unknown angiogenic triggers) may be released

by activation of epithelial and mast cells and initiates the
mobilization of EPCs from the bone marrow into the peripheral
circulation

 Homing signals recruit EPCs into the lungs

 EPCs switch the local environment from vascular quiescence to a pro-

angiogenic state

 Mediators released by EPCs either directly or indirectly via

interactions with vascular cells in the newly formed blood vessels
facilitate the recruitment and activation of pro-inflammatory cells
such as eosinophils
 Role of angiogenesis in asthma
 Bronchial vascular remodeling is a universal finding in
asthma

 The onset of neovascularization is before the recruitment

of inflammatory cells into the lungs (studies with mouse
models)

 Angiogenesis is an active component in the pathogenesis

of inflammation in asthma

 Does bronchial angiogenesis promote airway inflammation?

 Does airway inflammation trigger angiogenesis?

 Or are inflammation and angiogenesis codependent?

The “hygiene hypothesis”

Image adapted from: Busse W. & Lemanske R: N. Engl. J. Med. 2001;344(5):350-362

 Therapies

 No cure but can be controlled

 Major aims: reduce inflammation and increase

bronchodilation

 Medications:

 Long term
 Quick relief
 Bronchial thermoplasty

 Learning to recognize one’s own triggers and taking

steps to avoid them
 Learning objectives
 Define Asthma and summarize the most important symptoms of asthma.
 Explain the difference between a normal and an asthmatic bronchiole.
 Discuss some of the causes and the triggers of asthma.
 Describe the process of mast cell mediator release.
 Outline the process of development of asthma and focus on the immune
response contribution to the pathology – see video.
 Compare allergy with asthma.
 Advanced level question – name some of the cytokines that contribute
to the pathology of asthma and explain their action.
 Discuss briefly the metabolic pathway involving arachidonic acid and
production of prostaglandins/thromboxanes by COX1/COX2 and
leukotrienes by LOX. Why are aspirin/NSAIDs bad for asthma?
 Summarize the “hygiene hypothesis” and comment on its relation to
asthma – the role of Th1/Th2 balance.
 Name the two systems for blood supply to human lungs and describe
their role and direction of flow. What is the role of neovascularization?
 Advanced level question - Compare the pathology of asthma with that
induced by SARS-CoV-2 infection and CF.
Thank you