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262 Chapter 10 Allergies: rhinitis and urticaria
14) List the other drugs that Dorothy might be prescribed.
15) Explain the mechanism of action of monoclonal antibodies.
16) How do anticholinergic agents work in rhinitis? Which symptom do they control?
Dorothy is fed up and says she would like a cure. The doctor talks to her about immunotherapy.
She is eager to try, and is referred to the outpatient clinic.
17) Explain the theory behind immunotherapy.
PART 2
Dorothy’s friend Bradley also has many allergies. He doesn’t suffer from rhinitis but gets
urticaria when exposed to latex. This is a real problem because he is a dentist. Fortunately, he
usually has polyurethane gloves available. But on occasion the supply runs out and he is forced
to use latex ones.
18) What is urticaria? Which layer of the skin is affected?
19) Discuss the treatment options for urticaria.
20) If Bradley’s urticaria is particularly bad at night, what would be the best choice of treatment and why?
Chapter 11
Respiratory disease: asthma
and chronic obstructive
pulmonary disease (COPD)
Useful terms for this topic
Airway resistance: Resistance to the ow of air
though the respiratory tract during breathing.
Bronchiolar smooth muscle: The smooth muscle
wrapped around the bronchioles, which can relax or
contract to regulate the diameter of the airways.
Dyspnoea: Difculty in breathing.
Hyper-reactive airways: Inamed airways which
react to normally harmless substances.
Inflammatory mediators: Molecules released from
immune cells, such as mast cells, basophils, and
eosinophils, which promote the inammatory
response.
Obstructive respiratory disorder: Conditions
characterized by difculty breathing in.
Preventer medication: Corticosteroid drugs used
in asthma to tackle the underlying inammatory
process.
Restrictive respiratory disorder: Disorders
characterized by reduced lung capacity.
Reliever medication: Bronchodilator drugs used in
asthma to relieve symptoms.
Spasmogen: Stimulus that causes contraction of
bronchiolar smooth muscle.
Breathing is something we generally take for granted, but
imagine how distressing it must be to be unable to get air
into or out of your lungs. What it must be like to have to
stop every few steps to catch your breath, to be unable to
carry on a conversation without pausing for breath
between words, or, perhaps worse, having to carry an
oxygen canister with you for the rest of your life.
In most developed countries, conditions aecting the
lungs, such as asthma and chronic obstructive pulmonary
disease (COPD), contribute to a signicant burden of
illness. Most frustratingly, the incidence of COPD, the
fourth leading cause of death worldwide, would be
massively reduced if people didn’t smoke.
In this chapter we shall review the anatomy and physiology
of the lungs, and examine how they are altered by
molecular and cellular events that underlie the two most
common respiratory diseases, asthma and COPD. is
understanding is necessary in order to appreciate the
various targets for drugs that combat these conditions,
alleviating symptoms and/or modifying the disease
process itself. You can test your understanding in the
workbook at the end of this chapter, where these conditions
and their management are explored through our ctional
patients Chris, an asthmatic patient experiencing a are-up
of symptoms, and Ian, who has COPD.
11.1 Organization of the respiratory system
e respiratory system is composed of a complex series of
repeatedly branching tube structures starting at the nose
and mouth, where air enters, and terminating in the
alveoli (see below), where oxygen and carbon dioxide are
exchanged. Air is most usually inhaled through the nose,
and is conditioned (ltered, warmed, and humidied) in
264 Chapter 11 Respiratory disease: asthma and COPD
A
B
Parietal pleura
Pleural cavity
Secondary
bronchus
Primary
bronchus
Tertiary
bronchus
Bronchiole
Terminal
bronchiole
Anterior view
Larynx
Trachea
BRANCHING OF
BRONCHIAL TREE
Trachea
Primary bronchi
Secondary bronchi
Tertiary bronchi
Bronchioles
Terminal bronchioles
Carina
Diaphragm
Bronchiolar
smooth muscle
Elastin fibres
Bronchiole
Alveolus
Figure 11.1 The respiratory system.
A. The organization of the respiratory system showing the repeatedly-branching network of tube structures, from the trachea through
to the bronchioles. B. Detail of a bronchiole terminating in the alveoli where gas exchange takes place. Note the bands of smooth
muscle wrapped around the bronchiole.
the nasal cavities (see Chapter 10). Alternatively, air
enters through the mouth; conditioning does not occur in
the oral cavity, but larger volumes of air can enter, which
explains why we switch from nasal to oral inhalation
during exercise.
Air next passes through the pharynx, which conducts
both food and air, and which branches into the
oesophagus leading to the stomach, and the larynx which
is part of the airways. e epiglottis, a small ap of
cartilage at the opening to the larynx, prevents food or
drink from entering the lungs. e vocal cords are located
in the larynx and are protected by cartilage structures,
including the thyroid cartilage which, in males, protrudes
as the Adam’s apple. e nose, mouth, pharynx, and
larynx collectively comprise the upper airways.
e larynx opens into the trachea which marks the start of
the lower airways, depicted in Figure 11.1A. e trachea
splits into two branches, the primary bronchi (singular,
bronchus); the walls of both the trachea and bronchi are
supported by C-shaped cartilage rings. e bronchi enter
the lungs where they spread, branching repeatedly into
narrower and shorter tubes to form bronchioles, which
themselves branch again many times (see Figure 11.1A).
e walls of the bronchioles lack cartilage, but contain
elastin and smooth muscle (bronchiolar smooth
muscle). is muscle contracts or relaxes to regulate the
diameter of the bronchiolar tubules (see Figure 11.1B),
and is an important target for drugs used in the treatment
of lung disease. e bronchioles terminate in alveoli
(Figure 11.1B), tiny thin-walled sacs encircled by an
extremely dense network of capillaries. e alveoli are the
site of gas exchange; here, oxygen (O2) and carbon dioxide
(CO2) are rapidly exchanged by diusion across their thin
walls so as to enter or leave the blood. e walls are only a
single cell in thickness, comprised of epithelial type I
alveolar cells. To facilitate gas exchange, interspersed
with these cells are type II alveolar cells that produce
surfactant, a lipoprotein-containing secretion into which
the gases dissolve.
e movement of air into and out of the lungs
(respiration) is achieved by the inspiratory muscles, the
most important of which is the diaphragm, a sheet of
muscle that divides the thoracic cavity from the abdomen.
When relaxed, the diaphragm forms a dome which
protrudes up into the thoracic cavity. As illustrated in
Figure 11.2, at the start of breathing in the diaphragm
contracts and pulls down lower into the abdomen,
enlarging the volume of the thoracic cavity; the lungs
expand to ll the space. e pressure inside the lungs is
then less than atmospheric, and so air is drawn passively
into the lungs. When the pressure inside the lungs
matches atmospheric pressure, air no longer enters. As
the diaphragm relaxes and assumes its domed shape, the
thoracic cavity becomes smaller, and owing to the elastic
Breathing out
11.1 Organization of the respiratory system 265
By contrast, O2 levels must drop below 60% of normal
(hypoxaemia) before being detected by chemoreceptors.
11.1.1 Protective mechanisms in the
respiratory tract
e lungs are potentially exposed to a range of chemicals,
micro-organisms, and other air-borne particles, such as
dust in the inspired air. e respiratory tract therefore has
a number of important defence mechanisms. It is
innervated by sensory aerent nerves (both myelinated
Breathing in
Figure 11.2 Role of the diaphragm in respiration.
Contraction of the diaphragm, the major inspiratory muscle,
produces a negative pressure in the thoracic cavity which
causes the lungs to expand and air to be drawn in. As the
diaphragm relaxes it assumes its domed shape, the thoracic
cavity and lungs become smaller, and air leaves the lungs.
properties of their walls, the lungs return to their preexpanded size (elastic recoil). e air contained inside is
therefore compressed, and so the pressure inside the
lungs rises. When this happens, air will leave the lungs
until the pressure again matches atmospheric pressure.
is sequence of events describes quiet passive
breathing.
e diaphragm is aided by the intercostal muscles
between the ribs; their role is greater in more forceful
breathing. Here, other muscles including those in the
abdomen and neck contribute to enlarging the thoracic
cavity to a greater extent, thus drawing a larger volume of
air into the lungs.
Basic respiration is initiated and controlled by the
respiratory centre located in the medulla oblongata in the
brainstem. Breathing is mostly under autonomic control,
and we are therefore not conscious of the process. It is,
however, possible to inuence breathing voluntarily
because of connections between the medulla and the
cerebral cortex, as when we hold our breath. e rate of
ventilation is inuenced by concentrations of CO2 and O2
in arterial blood, detected by chemoreceptors in the
carotid and aortic bodies. Increases in CO2 levels, as seen
for example in emphysema (see Section 11.5), trigger a
reex increase in the depth and rate of respiration by
direct stimulation of the respiratory centre. is reex
response is initiated by only small increases in CO2 levels.
A-bres and unmyelinated C-bres) which are activated
by mechanical and chemical irritants in the air. e
receptors involved are members of the transient receptor
potential (TRP) class, and include TRPA1, which is
activated by air pollutants, and TRPV1, which is sensitive
to low extracellular pH and extremes of temperature, as
well as to capsaicin. (Receptors of this class are also
involved in the perception of pain; see Chapter 20,
Section 20.1.1.) e receptors are Ca
2 +
-permeant
non-selective cation channels; stimulation leads to an
inux of Ca
2 +,
activating the sensory nerve pathway which
connects with the medullary respiratory centre. By reex
action this causes a deep inspiration followed by a
forceful expiration, expelling the substance from the
lungs. TRP channel proteins have been shown to be
upregulated and/or to display increased sensitivity in
patients with asthma and COPD. ey are implicated in
the hypersensitivity of airways, and are therefore the
subject of research eorts as potential therapeutic targets.
In the nasal passages numerous tiny hairs trap particles
and prevent their further passage. e epithelial cells
which line the respiratory tract as far as the alveoli are
interspersed with mucus-producing goblet cells. In
addition, the epithelial cells express cilia, microscopic
nger-like projections that continually sweep the
secretions produced by goblet cells and bronchial glands
up towards the throat to be swallowed. Excessive
production of overly sticky mucus, as in patients with
cystic brosis or asthma, signicantly contributes to
respiratory disease, as does damage to the cilia caused by
smoking.
e lungs are also protected by cells of the immune
system.
• Phagocytic macrophages resident in the alveoli rapidly
engulf any pathogenic material that reaches them; they
too are damaged by cigarette smoke, as well as by air
pollutants.
266 Chapter 11 Respiratory disease: asthma and COPD
• Mast cells play an important protective role in healthy
lungs by initiating inammation in response to tissue
damage, and by providing immunity against bacterial
infection. e sustained release of pro-inammatory
mediators from mast cells in situations where
inammation is prolonged, as in asthma, contributes to
the pathophysiology of the disease.
11.1.2 Receptor targets in the
respiratory tract
Autonomic innervation of the respiratory tract is
predominantly parasympathetic, via the vagus nerve.
Parasympathetic ganglia (see Chapter 2, Section 2.2.2) are
located in the walls of the bronchi and bronchioles, from
where post-ganglionic bres connect with bronchiolar
smooth muscle and glands. e acetylcholine (ACh)
released acts on three types of muscarinic cholinergic
receptors, M1–M3. e M1 receptors are located at the
ganglia where they enhance neurotransmission. M2
receptors are inhibitory autoreceptors located on the
ACh-releasing nerve terminals. eir activation limits the
further release of ACh by negative feedback. ese
receptors are believed to be downregulated in asthmatic
patients, leading to increased ACh release and
contributing to hyper-reactivity of airways (see Section
11.3.1). e most pharmacologically important subtype of
muscarinic receptor is M3, which is present on smooth
muscle in the respiratory tract from the trachea through
to the terminal bronchioles.
M3 receptors are Gq-coupled GPCRs whose activation
leads via inositol 1,4,5-trisphosphate (IP3) to an increase
in cytosolic Ca
(DAG) to activation of protein kinase C (see Chapter 2,
Section 2.2.4). Ca
binding protein calmodulin (CaM), which in turn
activates the Ca
kinase (MLCK). is enzyme phosphorylates the
contractile protein, myosin light chain, allowing it to
interact with actin and therefore bringing about muscle
contraction (Figure 11.3). Dephosphorylation of the
myosin light chain is achieved by a further enzyme,
myosin phosphatase, which is inhibited by protein kinase
C. e net result of stimulation of the M3 receptors on
bronchiolar smooth muscle is contraction, resulting in
bronchoconstriction.
M3 receptors are also present on exocrine glands in the
lining of the respiratory tract, and their activation
enhances bronchial secretions.
2 +
concentration, and via diacylglycerol
2 +
forms a complex with the Ca
2 +
-sensitive enzyme myosin light chain
2 +
-
e second major pharmacological target in the
respiratory tract is the 2-adrenoceptor expressed by
bronchiolar smooth muscle cells. Considering their
sparse sympathetic innervation, the major physiological
agonist for these receptors is circulating adrenaline.
2-adrenoceptors are Gs-coupled receptors, and
activation stimulates adenylyl cyclase activity. e result
is an increase in the level of the second messenger, cyclic
AMP. is in turn activates protein kinase A (PKA) which
phosphorylates many substrates to bring about the
cellular response (Figure 11.3). e substrates/processes
aected include:
• MLCK, decreasing its sensitivity to Ca
2 +
, and therefore
its activity
• Myosin light chain phosphatase, increasing its ability to
dephosphorylate myosin light chains and so prevent
muscle contraction
• Activation of K + channels which leads to
hyperpolarization of the cell membrane. is in turn
reduces inux of Ca
2 +
through voltage-gated Ca
2 +
channels
• Stimulation of the Na +/K + -ATPase decreases
intracellular Na + concentration, and increases the Na +
gradient across the cell membrane. e Na + -Ca
2 +
exchanger is driven by this gradient; its activity is also
increased, favouring the extrusion of Ca
• Promoting uptake of Ca
2 +
into intracellular stores (the
2 +
sarcoplasmic reticulum; SR) via stimulation of the SR
2 +
Ca
pump. e mechanisms leading to the release of
2 +
Ca
from these stores are also inhibited
(phospholipase C and the IP3 receptor).
e net eect of the changes mediated by PKA is the
relaxation of the bronchiolar smooth muscle, resulting in
bronchodilatation.
As we shall see later, 2-adrenoceptor agonists are central
to the treatment of asthma. e therapeutic response to
these agents may not be governed solely by their eects
on bronchiolar smooth muscle, but may reect actions on
additional cells and processes. For example, ciliary beat
frequency may be enhanced by activation of 2adrenoceptors on epithelial cells. In this respect, it is also
important to note that 2-adrenoceptors are present on a
range of immune cells including T-lymphocytes,
eosinophils, and mast cells. e processes regulated by
activation of these receptors are central to the
inammatory response, such as release of potent
inammatory mediators (e.g. histamine from mast cells
11.2 Common airway diseases: asthma and chronic obstructive pulmonary disease (COPD) 267
Adr
ACh
β
2
M
3
PLC
cAMP
+
K
PKA
2+
Ca
+
K
+
Na
MLCP
My
MLCK
SR
Ca
IP
3
IP
R
3
2+
Ca
2+
CaM
Ca-CaM
My-P
Contraction
Figure 11.3 Signal transduction pathways involved in the relaxation and
contraction of bronchiolar smooth muscle.
Acetylcholine (ACh), acting at Gq-coupled M3 receptors, activates phospholipase C to
generate inositol trisphosphate (IP3) and diacylglycerol (not shown). IP3 acts at ligandgated Ca
complex with calmodulin (CaM), which activates myosin light chain kinase (MLCK). The
enzyme phosphorylates myosin (My), enabling it to interact with actin and so bring about
contraction of the smooth muscle cell. Adrenaline (Adr), acting at Gs-coupled 2adrenoceptors, activates adenylyl cyclase to increase cyclic AMP (cAMP) levels. Protein
kinase A (PKA) is then stimulated. PKA inhibits MLCK activity, as well as activating
myosin light chain phosphatase (MLCP) to dephosphorylate myosin; both actions
prevent contraction of the smooth muscle. Additionally, PKA reduces cytosolic Ca
levels through a number of mechanisms as shown. PKA also affects fluxes of K+ and Na
across the plasma membrane; the consequences of these changes are described in the
text. Mechanisms that are stimulated by PKA are indicated by solid lines, and those that
are inhibited are indicated by dotted lines.
2 +
channels on the sarcoplasmic reticulum (SR) to release Ca
2 +
. This forms a
2 +
+
resident in the lungs; see Section 11.3.1). As yet though, it
is unclear whether these responses contribute to the
Section P3.2 in the Introduction to Part 3 of this book), but
are not themselves targets for anti-asthma drugs.
clinical eects of 2-adrenoceptor agonists.
Bronchiolar smooth muscle cells express H1 histamine
receptors, Gq-coupled receptors which when activated
elicit bronchoconstriction. ese receptors are central to
the pathogenesis of asthma (see Section 11.3.1, and
1 Evidence from clinical trials has shown that at doses that do not cause
unacceptable side eects, both rst- and second-generation
antihistamines do not improve symptoms of asthma. is is presumed to
be because of the range of other mediators, notably leukotrienes, that are
involved in pathogenesis of the condition.
11.2 Common airway diseases: asthma and chronic
obstructive pulmonary disease (COPD)
Asthma and COPD are by far the most prevalent respiratory
diseases. Both are obstructive disorders (see Box 11.2 in
Section 11.3.2) and share some common symptoms and
treatments. Nonetheless they are distinct medical
conditions, each with distinguishing causes and features
(Table 11.1), and are therefore considered separately.
1
268 Chapter 11 Respiratory disease: asthma and COPD
Table 11.1 Comparison of the clinical features of asthma and COPD (adapted from NICE
Guidelines 2010)
Asthma COPD
Usual age of onset Childhood Middle age
Triggers/causes of the disease Allergens
Degree of reversibility of airway narrowing ReversibleaOnly partially reversible
Time course of symptoms Episodic Gradually progressive
Breathlessness Variable Persistent and progressive
Night-time waking with breathlessness and/or
wheeze
Significant variability in symptoms within the
same day, or from one day to the next
a
Except in status asthmaticus, a very severe and potentially fatal form of asthma, where airway narrowing may
not be reversible.
11.3 Asthma
Exercise
Common Uncommon
Common Uncommon
Smoking
Asthma is the most common lung condition, aecting
10–15% of children and 8–10% of adults. e Global
Initiative for Asthma (GINA), an international
collaboration involving the World Health Organization,
estimates that over 300 million people are aected
worldwide. Asthma is associated with signicant
morbidity, and a considerable number of patients suer
frequent, including daily, attacks. ese attacks can
disrupt sleep, work, or schooling, and make activities
such as sport dicult. In its most severe form, asthma can
lead to a condition called status asthmaticus, which is
unresponsive to normal bronchodilator therapy and can
be fatal.
e drugs used in the treatment of asthma are eective,
yet it remains a poorly controlled disease. In the UK alone
around 1400 people die each year from the condition. It
has been estimated that most of these deaths (perhaps up
to 90%) would be avoided if drugs were used correctly.
Pharmacists and healthcare professionals have an
important role in counselling patients and carers on the
correct and appropriate use of drugs. is necessitates an
understanding of the basis of the disease itself, and where
the drugs used in its management have their eects.
11.3.1 Pathogenesis of asthma
e complex pathogenesis of asthma involves an array of
processes, cells, and chemical mediators, many of which
are the targets for drug therapy. Asthma is an
inammatory condition characterized by recurrent
reversible obstruction of the airways, often triggered by
normally innocuous stimuli. (e underlying
inammatory processes are described in Section P3.2 in
the Introduction to Part 3 of this book.) An asthma attack
can broadly be divided into an immediate/early phase
and a delayed/late phase (Box 11.1). In the immediate
phase bronchoconstriction dominates, largely as a result
of mediators released by degranulation of mast cells.
• Histamine mediates bronchoconstriction by activating
Gq-coupled H1 receptors on the bronchiolar smooth
muscle cells. It is a powerful inammatory mediator,
and causes local vasodilatation and increased vascular
permeability, leading to oedema.
• e cysteinyl leukotrienes C4 and D4 increase mucus
secretion and are potent spasmogens, inducing
contraction of bronchiolar smooth muscle. eir
receptors are antagonized by the ‘lukast’ group of drugs
used in asthma (see Section 11.4.3).
• e related non-cysteinyl leukotriene B4 is a potent
chemo-attractant, drawing in other immune cells to
encourage further release of chemical mediators.
• Prostaglandin D2, acting through Gs-coupled DP1
receptors, leads to contraction of bronchiolar smooth
muscle, and to increased vascular permeability and
hence oedema.
e combined action of these local chemical mediators
gives rise to the bronchoconstriction which characterizes
11.3 Asthma 269
Box 11.1
Early and late phases of an asthma attack
Late phase
Antigen presenting cell
Antigen
1
CD
4
T-cell
2
Th0
cell
Corticosteroids
Cromolyns
Mononuclear
cell
6
Eosinophils
inammation
S
S
m
u
c
o
m
b
u
o
M
s
a
h
m
t
o
u
s
c
l
e
o
c
s
u
a
Th2
cell
= IgE antibody
Figure a
1. Antigens that enter the lung are captured and processed by antigen-presenting dendritic cells (APCs) that line the
respiratory tract. The APCs interact with naive T-cells.
2. This interaction stimulates the generation and proliferation of T-helper 0 (Th0) and T-helper 2 (Th2) cells from naive T-cells.
Th2 cells release a number of cytokines, including interleukins IL-4, IL-5, and IL-9.
3. The cytokines coordinate the release of immunoglobulin E (IgE) antibodies by plasma cells (P cells), as well as attracting
other inflammatory cells, particularly eosinophils. The IgE binds to mast cells to activate them.
4. Activated mast cells release a range of inflammatory mediators.
5. Histamine and cysteinyl leukotrienes C4 and D4 (LT-C4, LT-D4) released from mast cells are potent spasmogens responsible
for the bronchoconstriction characterizing the early phase of an asthma attack. Mucus secretions are also increased.
6. Inflammatory cells, including eosinophils and mononuclear cells, migrate into the mucosa and submucosa attracted by
chemokines and chemotaxins from mast cells. Eosinophils release toxic proteins that damage the epithelium. The
bronchiolar smooth muscle cells are stimulated to grow and proliferate by growth factors released from immune cells, and
from the muscle cells themselves, contributing to airway remodelling.
IL-4
IL-5
IL-9
B-cells P-cells
3
Chemokines
Chemotaxins
Anti-IgE AB
5
Histamine
LTC
4
LTD
4
Mast cells
4
Early phase
bronchoconstriction
β2-adrenoceptor agonists
Muscarinic antagonists
Leukotriene receptor
antagonists
Cromolyns
Theophylline
270 Chapter 11 Respiratory disease: asthma and COPD
Risk factors
Genetics (e.g. family history, atopy)
Triggers (e.g. allergens, pollution, drugs)
Attraction of inflammatory cells
Mononuclear cells
Eosinophils
Bronchial inflammation
Bronchial hypersensitivity
Figure 11.4 Processes in the pathogenesis of asthma.
Release of mediators
Histamine
Leukotriene B
Bronchial contraction
Asthma symptoms
Shortness of breath
Wheeze
Cough
Chest tightness
4
the early phase, but also sets in train the inammatory
events in the late phase. Here, the actions of inammatory
cells dominate, including T-helper 2 (2) cells which
release interleukins. ese are cytokines, local protein
mediators which promote the inammatory response by
drawing in more immune cells which themselves add to
the cascading events by releasing further cytokines. A
central role is lled by eosinophils—polymorphonuclear
cells which release a range of leukotrienes and the toxic
proteins major basic protein, eosinophil peroxidase,
eosinophil cationic protein, and eosinophil-derived
neurotoxin. Together these substances cause damage and
loss of epithelium. ese interlinked and self-promoting
events collectively result in inammation and hyperreactivity of the asthmatic airways (Figure 11.4). e
hyper-reactivity is believed to arise, at least in part, from
increased expression of epithelial TRPV1 receptors,
leading to sensitization of sensory nerves (see Section
11.1.1).
ese events in the late phase of asthma lead to structural
changes to the airways including:
• hypertrophy and hyperplasia of the smooth muscles
surrounding the bronchioles, brought about by growth
factors released from inammatory cells
• increased number of blood vessels
• thickening of the airway walls due to oedema
• increased number and size of bronchial glands and
goblet cells, resulting in increased volume and viscosity
of mucus secretions which leads to decreased
mucociliary clearance, and mucous plugging.
e changes which occur in asthmatic airways compared
with those in a healthy subject are depicted in Figure 11.5.
11.3 Asthma 271
A
Relaxed
bronchiolar
smooth muscle
Elastin bre
Airway lumen
Airway wall
Figure 11.5 Comparison of (A) healthy with (B) asthmatic bronchioles.
The inflammatory response in asthma leads to remodelling of the airways which show thickened walls due to
oedema, and have a greater muscle content. An increased volume of thick mucus leads to the formation of mucus
plugs.
B
Contracted
bronchiolar
smooth muscle
Narrowed airway
lumen
Thick mucus plug
Thickened airway
wall - greater smooth
muscle content,
oedema, and increased
number of blood vessels
11.3.2 Asthma symptoms and diagnosis
e exact cause of asthma is not fully understood, but
involves a combination of both environmental and
genetic factors. It is characterized by bronchoconstriction,
inammation, and increased mucus secretions, which
together lead to narrowing of the airways. e obstruction
to the ow of air results in the characteristic symptoms of
wheezing, cough (often at night), chest tightness, and
diculty in breathing (dyspnoea). If you want to know
how it feels to have asthma, take a drinking straw, block
your nose, and try to breathe in and out through the
straw. (Don’t try this if you actually have asthma!)
Asthma is diagnosed through a combination of
symptoms, demonstration of reversible airow
obstruction with bronchodilators, and standard measures
of lung function (see Box 11.2).
11.3.3 Types of asthma and triggers
Asthma can be divided into two types depending on the
nature of its triggers. e most common is allergic asthma
(also called atopic or extrinsic asthma), which is
associated with a range of allergens to which the person
has previously been sensitized. Common examples
include pollens, house dust mites, animal hair and saliva,
and certain foodstus such as shellsh or yeast. e
condition characteristically starts in childhood, and
patients often have a personal or family history of allergic
rhinitis and/or eczema.
In patients with non-allergic (intrinsic) asthma, a number
of other substances and conditions can trigger an asthma
attack, including exercise, extremes of environmental
temperature, emotional stress, viral infections, and
hormones. ere is mounting evidence that non-allergic
asthma may have a dierent spectrum of immune cell
involvement, with neutrophils rather than eosinophils
being central to its pathogenesis. It is worth noting that
non-allergic non-eosinophilic asthma does not appear to
respond as well to inhaled corticosteroids as allergic
eosinophilic asthma (see Section 11.4.2).
Asthma can also be precipitated by a number of
medicines. Non-selective -adrenoceptor antagonists
(-blockers) used in the treatment of hypertension can