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Explain the pathogenesis causing the clinical manifestation of with which peter present.

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acute bronchitis, 73

acute respiratory distress syndrome,

730
adenocarcinoma, 739
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atelectasis, 75

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chronic bronchitis, 721
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disease (COPD), 7

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croup, 743
cyanosis, 756
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dyspnoea,

755

emphysema, 723
empyema, 753
eupnoea, 756
haemoptysis, 756
hypercapnia, 752
hyperventilation, 756
hypoventilation, 755
hypoxaemia, 7

influenza, 736
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obstructive sleep apnoea, 742
pertussis, 738
pleural effusion, 753
pneumoconiosis, 732
pneumonia, 7

pneumothorax, 752
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pulmonary oedema, 749
small cell carcinoma, 740
squamous cell carcinoma, 739
status asthmaticus, 717
sudden infant death syndrome

(SIDS), 746
TNM classification, 741
tubercles, 734
tuberculosis, 734Introduction, 711

Disorders of the pulmonary system, 711
Obstructive airway diseases, 711
Restrictive airway diseases, 729
Infections of the pulmonary system, 732
Pneumonia, 733
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Influenza, 736
Lung cancer, 738
Types of lung cancer, 738

Obstructive sleep apnoea, 742
Alterations of pulmonary blood flow and

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749
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755

C h a p t e r o u t l i n e

Alterations of pulmonary
function across the life span
Vanessa Marie McDonald, Steven Maltby and
Darrin Penola

C H A P T E R

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CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 711

conditions. In this way, you can learn about the
pathophysiology of the pulmonary conditions and so
understand how these alterations manifest in individuals.

Disorders of the
pulmonary system
Obstructive airway diseases
Obstructive airway diseases are characterised by airflow
obstruction or limitation that causes more difficulty during
expiration. More force — that is, the use of the accessory
muscles of expiration — is required to expire a given volume
of air or emptying of the lungs is slowed, or both. In adults
and children, the major obstructive airway disease is asthma,
with chronic obstructive pulmonary disease (COPD) also
highly prevalent in the adult population. Airflow obstruction
is usually variable in asthma, whereas in COPD it is less
reversible. The unifying symptom of obstructive airway
diseases is dyspnoea (difficulty breathing or breathlessness).
Manifestations of obstructive airway diseases include
an increased work of breathing, ventilation/perfusion
mismatching, a decreased forced expiratory volume in one
second (FEV1) and decreased FEV1/forced vital capacity
(FVC) ratio.

Obstructive airway diseases are prevalent in the
Australian and New Zealand populations leading to a high
disease burden. In the following section we examine the
pathophysiology of asthma in both children and adults, to
provide a more thorough understanding of the disease.

Asthma
There are large variations in the incidence and prevalence
of asthma according to geographical regions. Worldwide
it is estimated that over 300 million people have asthma
and there is likely to be a marked increase in this number
over the next two decades as modern lifestyles and
urbanisation occur in developing countries.3 Rates of asthma
are higher in Westernised societies than developing countries
and indeed the prevalence of asthma in Australia and New
Zealand is high by international standards.3–5

In Australia, more than two million people have asthma
(10.2% of the population), with slightly higher rates in
children compared to adults.6 In childhood more males
than females have asthma; however, this trend reverses in
adulthood, with more females than males having asthma.5

Unfortunately, as with so many chronic diseases, the
Indigenous populations in both Australia and New Zealand
have higher rates of asthma compared to the non-Indigenous
populations: in New Zealand the prevalence of asthma in
Māori and Pacific Islander adults is greater than in the
non-Indigenous population4,5 and in Australia asthma is
the second most common illness, affecting greater than
60% of the Indigenous population compared to
non-Indigenous.5

While mortality rates from asthma decreased through
to the end of the 20th century, rates remained stable between
2004–2013 in Australia, at around 1.5 deaths per 100 000

Introduction
At some stage everyone experiences an alteration to the
pulmonary system. This may range from a minor respiratory
illness through to chronic lung diseases and cancers. The
common cold, a mild upper respiratory tract infection
arising from several different viruses, is one of the most
familiar pulmonary infections and most people experience
one or two infections each year. Often more serious is the
impact of influenza, commonly referred to as the ‘flu’, with
an estimated 5–20% of the Australian and New Zealand
populations infected each year and up to half a million
deaths worldwide.1

Pulmonary diseases and disorders can severely limit an
individual’s ability to perform activities of daily living and
result in frequent hospitalisations. Moreover, alterations to
the pulmonary system contribute significantly to mortality
rates in Australia and New Zealand. The lungs, with their
large surface area, are constantly exposed to the external
environment. Therefore, lung disease is greatly influenced
by conditions of the environment, occupation and personal
and social habits. For instance, individuals who smoke are
known to be at a greater risk of lung conditions compared
to non-smokers. Symptoms of lung disease are common
and associated not only with primary lung disorders but
also with diseases of other organ systems.

Alterations of respiratory function in children are
influenced by physiological maturation as a function of
age, genetics and environmental conditions. A variety of
upper and lower airway infections can cause respiratory
problems or play a role in the pathogenesis of more chronic
pulmonary diseases. Infants, especially premature infants,
may present special problems because of the immaturity
of their lung, airway and chest wall structures, as well as
the immaturity of pulmonary homeostasis (e.g. a lack of
surfactant production) and immunological immaturity.
Immunisation and attentive healthcare can greatly reduce
the incidence and severity of pulmonary disorders in
children. The lungs continue to mature up until about 20
years of age for females and 25 years for males. Thereafter
ageing is associated with a progressive decline in lung
function resulting in both airflow limitation and reduced
exercise capacity. The morphological and immunological
changes that occur during ageing can lead to increased air
trapping and a reduction in chest wall compliance causing
an increased work of breathing for older individuals.2

Pulmonary disease is often classified using different
categories and may be described as acute or chronic,
obstructive or restrictive, or infectious or non-infectious.
Because skillful and knowledgeable clinical practice plays
a major role in the management of pulmonary conditions,
healthcare professionals who have a clear understanding
of the pathophysiology of common pulmonary disorders
can provide more optimal management of affected
individuals with the goal of improving outcomes.

This chapter examines the more common alterations to
the pulmonary system and then provides detailed information
about the signs and symptoms that arise from these

712 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

The airflow limitation resulting from these physiological
changes is episodic and usually reversible. The clinical
pattern of asthma is variable, and the immunological
processes underlying asthma pathophysiology also vary
between individuals. Classically, asthma is associated
with a predominance of CD4+ T lymphocyte cells and the
release of type 2 helper T cell (TH2)-associated mediators
such as IL-4, IL-5 and IL-13 and airway eosinophilia.
Alternatively, non-TH2 asthma includes a predominance
of TH1 (and associated IFNγ), and TH17 (with associated
IL-17 cytokine production) and neutrophilic airway
inflammation.15 Assessment of the inflammatory cells from
sputum can identify individuals with differing patterns
of airway inflammation, which is becoming increasingly
important for the integration of targeted therapies (such as
anti-IgE), which are only effective in subsets of patients.16
Remodelling of the airway structures also occurs in the
long term.

In asthma, the airways respond in an abnormal,
exaggerated way to inflammatory mediators, such as an
allergen or irritants or triggers like pollution, exercise, cold air
or respiratory infection (bacterial or viral). Allergic responses
can be initiated by a type I hypersensitivity reaction (see
Chapter 15). Exposure to allergens or irritants results in a
cascade of events, beginning with mast cell degranulation
and the release of multiple inflammatory mediators (see
Fig. 25.1). Some of the most important mediators that
are released during an acute allergic asthmatic episode
are histamine, interleukins, prostaglandins, leukotrienes
and nitric oxide. The vasoactive effects of these cytokines
include vasodilation and increased capillary permeability.
This causes an increase in blood flow to the area, and
inflammatory cells and chemicals move through the cells into
the interstitial tissue. Alternatively, triggers such as bacterial
or viral infection or exposure to pollutants can activate lung
macrophages and resident innate immune cells. Activation
results in local release of pro-inflammatory cytokines and
tissue inflammation. In both cases, chemotactic factors
(chemicals that attract inflammatory cells to the site of
inflammation) are produced, which result in bronchial
infiltration by eosinophils, neutrophils, and lymphocytes
(different types of white blood cells). These activated
immune cells, particularly eosinophils, release a variety
of chemicals that contribute to inflammation and tissue
damage. The resulting inflammatory process produces
bronchial smooth muscle spasm, vascular congestion,
oedema formation, production of thick mucus, impaired
mucociliary function, thickening of airway walls and
increased bronchial hyperresponsiveness (see Fig. 25.2). In
addition, there is alteration to the normal autonomic control
of bronchial smooth muscle because the production of
neuropeptides (small protein-like substances that are released
by neurons to communicate with other neurons) leads to
acetylcholine-mediated bronchospasm. These changes,
combined with epithelial cell damage caused by immune
cell infiltration, produce airway hyperresponsiveness and
obstruction and, if untreated, can lead to long-term airway
damage that is irreversible.

population.7 Furthermore, Australian asthma mortality rates
remain high by international standards,8 and while asthma
deaths continue to occur in all age groups, the risk of dying
from asthma increases with age.9 In 2015 there were 421
deaths in Australia due to asthma, representing 0.3% of all
deaths that year.9 Rates of hospitalisation are fairly low,
with approximately 38 000 hospitalisations in 2011–12 or
0.4% of all hospitalisations in Australia,10 with less than
5% of adults and children with asthma being hospitalised
for episodes of acute asthma. Nonetheless, the economic
costs are high, as the direct costs associated with asthma
are estimated at $1.2 billion, total economic costs (including
disability and premature mortality) at $3.3 billion and total
burden of disease costs of $23.7 billion.11

Asthma is likely to result from a complex interaction
of genetic and environmental components. It can be defined
as:

… a heterogeneous disease [meaning that it
varies considerably for different people], usually
characterized by chronic airway inflammation. It is
defined by the history of respiratory symptoms such
as wheeze, shortness of breath, chest tightness and
cough that vary over time and in intensity, together
with variable expiratory airflow limitation.12

Asthma is a familial disorder, and many genes have
been identified that may play a role in the susceptibility
and pathogenesis of asthma, including those that influence
the production of interleukins IL-4, IL-5 and IL-13,
immunoglobin E (IgE), eosinophils, mast cells, β(beta)-
adrenergic receptors (for the stress response using adrenaline)
and airway hyperresponsiveness (the ability of the airways
to constrict more easily and to a greater degree in response
to a bronchoconstrictor or stimulus).

Risk factors for asthma, in addition to family history,
include allergen exposure, living in urban areas, exposure
to air pollution and cigarette smoke, recurrent respiratory
viral infections and other allergic diseases, such as allergic
rhinitis.13 There is considerable evidence that exposure to
high levels of certain allergens during childhood increases
the risk for asthma. Furthermore, decreased exposure to
certain infectious organisms appears to create an
immunological imbalance that favours the development of
allergy and asthma. This complex relationship has been
called the hygiene hypothesis, in which it is thought that
living with low levels of infectious organisms can make the
immune system particularly prone to the development of
allergy.14 People living in urban environments have been
shown to have a higher disposition to asthma compared
to those who reside in rural areas. The likely exposure to
air pollution combined with decreased exercise also play
a role in the increasing prevalence of asthma.13

PAT H O P HYS I O LO G Y
The principal characteristics of asthma are airway
inflammation, airway hyperresponsiveness and mucus
hypersecretion resulting in airflow obstruction, leading to
symptoms of dyspnoea, cough, chest tightness and wheeze.12

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 713

For acute allergen-induced asthma, the paradigm of the
early asthmatic response remains useful (see Fig. 25.3A).
This begins immediately after exposure and lasts up to
2 hours. The allergen binds to preformed immunoglobin
E (IgE) on the surface of mucosal mast cells, and cross-linking
of these IgE molecules triggers degranulation of the mast
cells, releasing mediators such as histamine, leukotrienes,
prostaglandin D2, platelet-activating factor and certain
cytokines. These mediators cause airway smooth muscle
constriction (bronchospasm), increased vascular permeability
(mucosal oedema) and mucus secretion.

The late asthmatic response starts 4–8 hours after the
initial exposure and may persist for up to 24 hours (see
Fig. 25.3B). The response is characterised by inflammatory

Examination of postmortem lung specimens of
individuals who have died from asthma reveals abnormalities
consistent with both acute and chronic changes in the
airways. These include extensive mucus plugging, mucosal
oedema and denudation of bronchial and bronchiolar
epithelium (loss of epithelium). Eosinophilia (an increased
amount of eosinophils) is present in the submucosa in some
cases, and a multicellular inflammatory infiltrate accumulates
in the airways. Thickening of the basement membrane,
airway smooth muscle hypertrophy and mucous gland
hypertrophy are often noted, sometimes even in pathology
specimens from people with mild asthma, providing
evidence that there may be long-term airway structural
changes associated with asthma.

C
O

N
C

T M

initiator
mediators
dysfunctional process

Colour code

Bronchial hyperresponsiveness
Airway obstruction

Allergen or irritant exposure

promotes

releasesrelease release

act to

which

increases

results

results in

leads to

leads to
leads to

produces

over
time

causes

cause

Mast cell degranulation

Chemotactic mediators Chemical mediator

Stimulate nerve
terminal endings

Release of
neurotransmitters

Cellular in�ltration
(neutrophils, lymphocytes, eosinophil

)

Autonomic
dysregulation

Immune activation
(IL-4, IgE production)

Vasoactive mediators

Vasodilation
Increased capillary permeability

Bronchospasm
Vascular congestion

Mucus secretion

Impaired mucociliary function
Thickening of airway walls

Increased contractile response of
bronchial smooth muscle

Release of
neuropeptides

Epithelial desquamation (removal of epithelial lining)
and �brosis (excessive connective tissue)

FIGURE 25.1

The pathophysiology of asthma.
A concept map outlining the effects of exposure to an allergen or irritant, which causes an inflammatory cascade leading to acute and
chronic airway dysfunction.

714 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

severe, the number of alveoli being adequately ventilated
and perfused decreases. Air trapping continues to worsen
and the work of breathing increases further, leading to
hypoventilation (decreased tidal volume), carbon dioxide
retention and respiratory acidosis (from the reduction in
carbon dioxide removal). Respiratory acidosis signals
respiratory failure (Fig. 25.4 summarises these steps).

C L I N I C A L MA N I F E S TAT I O N

When asthma is well controlled individuals should experience
few if any symptoms and pulmonary function tests will
usually be within normal limits. However, individuals
with asthma are at risk of acute exacerbations, usually
as a result of exposure to triggers that cause an airway
inflammatory response and acute bronchoconstriction.
These may include exposure to allergens, infections,
occupational exposures, tobacco smoke or from treatment
non-adherence. Further, 5–10% of individuals with asthma
have severe disease which requires high-dose therapy to
control, or remains uncontrolled despite treatment.17
Exacerbations are defined as ‘events that require urgent
action on the part of the patient and physician to prevent
a serious outcome, such as hospitalization or death from
asthma’.18 During an exacerbation, the individual may
experience bronchoconstriction, expiratory wheezing,
dyspnoea, cough, prolonged expiration, tachycardia and
tachypnoea (increased ventilatory rate). Severe episodes
involve the accessory muscles of ventilation and wheezing
is heard during both inspiration and expiration. Pulsus
paradoxus (an exaggerated decrease in systolic blood
pressure during inspiration) may be noted. Lung function
measured by spirometry is reduced. Because the severity
of blood gas alterations is difficult to evaluate by clinical

cell recruitment (neutrophils, eosinophils, basophils,
lymphocytes) that was triggered earlier by chemotactic
factors and endothelial adhesion molecules (molecules
that attach to the endothelial). Another wave of mediator
release occurs, again causing bronchospasm, oedema
and mucus secretion. Epithelial damage and impaired
mucociliary function (the sweeping ability of the cilia lining
the airways) may be seen following immune cell activation
within the lungs, including production of toxic mediators
by eosinophils, neutrophils and activated macrophages.
This local injury stimulates local nerve endings, which
may aggravate bronchoconstriction and mucus secretion
through autonomic pathways.

In chronic asthma, some of these mechanisms may
be operational on an ongoing basis. There are increased
numbers of inflammatory cells, which may lead to long-term
changes such as goblet cell hyperplasia (abnormally
increased number of mucus-secreting cells) and airway
wall remodelling (subepithelial fibrosis, smooth muscle
hypertrophy).

Airway obstruction increases resistance to airflow and
decreases flow rates, primarily expiratory flow. For instance,
a 10% reduction in airway calibre leads to a 2% increase
in resistance. Impaired exhalation causes air trapping and
hyperinflation distal to obstructions and increases the work
of breathing. Intrapleural and alveolar gas pressures rise
and cause decreased perfusion of the alveoli. These changes
lead to uneven ventilation–perfusion relationships causing
hypoxaemia (a reduction in oxygen levels in the blood).
Hyperventilation is triggered by lung receptors responding
to the hyperinflation and causes a decrease in carbon dioxide
levels in the blood (PaCO2) and increased pH (which results
in respiratory alkalosis). As the obstruction becomes more

Pulmonary artery
Cartilage Submucosal

gland

Basement
membrane

Epithelium

Goblet cell

Alveoli

Respiratory
bronchioles

Bronchioles

Mast cell

Parasympathetic
nerve

Smooth
muscle

Smooth muscle

constriction

Mucus
plug

Hyperinflation
of alveoli

Mucus
accumulation

Degranulation
of mast cell

FIGURE 25.2

Changes in airways due to asthma.
A Normal lung with clear airways. B Thick mucus, mucosal oedema and smooth muscle spasm causing obstruction of small airways
occurs in asthma, breathing becomes laboured and expiration is difficult due to the airway restrictions.

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 715

altered by regional hypoxic vasoconstriction, as well as the
effect of increased intraalveolar pressure (caused by
hyperinflation) to decrease perfusion of the alveolar
capillaries. Typically, the ventilatory rate (commonly referred
to as the respiratory rate in clinical environments) is elevated
to compensate for hypoxaemia, with reduced minute
ventilation because of increased airway resistance and lung
hyperinflation. Thus, the carbon dioxide level is low
(30–35 mmHg compared to the normal level of
35–45 mmHg) or can be normal. Retention of carbon
dioxide is a late finding and reflects inadequate alveolar
ventilation and increased functional dead space as little air

signs alone, arterial blood gas levels should be measured if
oxygen saturation falls below 90%. The usual findings are
hypoxaemia with an associated respiratory alkalosis. The
severity of acute asthmatic episodes is outlined in Table 25.1.

The typical arterial blood gas abnormalities seen in acute
asthma are hypoxaemia, hypocapnia (low blood carbon
dioxide levels) and respiratory alkalosis (a pH level above
7.45). As bronchial obstruction is non-uniform, ventilation
becomes uneven, causing ventilation–perfusion mismatch
and further hypoxaemia. The degree of hypoxaemia is usually
mild; however, arterial saturations of less than 90% indicate
severe airway obstruction. Pulmonary circulation may be

Mast cell

Antigen

Dendritic
cell

Goblet cell
Mast cell

Antigen entry to airway

Mast cell degranulation
and release of
mediators

Mediator
e�ects

Airway smooth
muscle constriction

Vascular
leak of
�uid

Mucus secretion
Smooth muscle

Eosinophil Neutrophil

Vascular
cell adhesion
moleculeTH2 cell

33
B
A
B

FIGURE 25.3

Asthmatic responses at a cellular level.
A Early asthmatic response. 1 Inhaled antigen enters the airway and binds to IgE on mast cells. 2 Mast cells degranulate and release
mediators such as histamine, prostaglandin D2 and platelet-activating factor, which promotes inflammation. 3 These chemicals open
junctions between cells, allowing the allergen to penetrate below the epithelial surface, which induces active bronchospasm, oedema and
mucus secretion. At the same time, as shown on the left, antigen may be received by dendritic cells and later present to T helper (TH)
lymphocytes in the airway mucosa (see B). B Late asthmatic response. There are areas of epithelial damage caused at least in part by
toxicity of eosinophil. Local T lymphocytes produce IL-4 and IL-13, which promote switching of B cells to favour IgE production, and IL-3,
IL-5 and granulocyte-macrophage colony-stimulating factor, which encourage eosinophil differentiation and survival.

716 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

TABLE 25.1 Assessment of acute asthma episodes in adults

FINDINGS MILD MODERATE SEVERE AND LIFE THREATENING

Physical exhaustion No No Yes

Paradoxical chest wall movement may
be present

Talks in Sentences Phrases Words

Pulse rate < 100/min 100–120/min More than 120/min Pulsus paradoxus Not palpable May be palpable Palpable

Central cyanosis Absent May be present Likely to be present

Wheeze intensity Variable Moderate to loud Often quiet

PEF More than 75% predicted
(or best if known)

50–75% predicted (or best
if known)

Less than 50% predicted (or best if
known) or less than 100 L/min

FEV1 More than 75% predicted 50–75% predicted Less than 50% predicted or less than 1 L

Oximetry on presentation Less than 90%

Cyanosis may be present

Arterial blood gases Not necessary Necessary if initial response
poor

Necessary

Other investigations Not required May be required Check for hypokalaemia

Chest x-ray to exclude other pathology
(i.e. infection, pneumothorax)

FEV1 = forced expiratory volume in first second; PEF = peak expiratory flow

C
O
N
C

E
P

T
M

A
P Oedema, mucus, muscle spasm

causes
causes
causes
causes

causes causes

causes
causes
leads to

leads to
results in

results in
results in

Resistance to airflow

Impaired expiration

Air trapping

Alveolar hyperinflation

Uneven ventilation/perfusion

Decreased alveolar
ventilation

Decreased pulmonary
blood flow

Impaired gas exchange

Hypoxaemia

Hypercapnia

Respiratory failure

FIGURE 25.4

Asthma airway obstruction cascade.
The oedema, mucus and mucus spasm cause resistance to airflow, such that air remains trapped in the lungs. As a result, there are
impairments in gas exchange that can lead to respiratory failure.

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 717

determines how much and how quickly air can be expired
from the lungs. The key variables measured during
spirometry are forced expiratory volume in the first second
(FEV1), forced vital capacity (FVC), FEV1/FVC ratio and
peak expiratory flow (PEF) (see Table 25.2). Spirometry
may be used to diagnose airway obstruction, assess its
severity and prognosis and to demonstrate any reversible
effect. An example of airway obstruction compared to
normal spirometry is provided in Fig. 25.5, including the
response to treatment using bronchodilators.

In children less than 5 years of age spirometry is not
recommended. In such cases, a history from the parents is
crucial. Between episodes, the diagnosis of asthma is

is being moved. Alterations of pH homeostasis usually start
with respiratory alkalosis (pH greater than 7.45) caused by
hyperventilation, which literally ‘blows off ’ carbon dioxide.
With severe airway obstruction, the end result of the
pathophysiological processes may be respiratory failure,
with acute carbon dioxide retention and respiratory acidosis
(pH less than 7.35).

When bronchospasm worsens during a severe asthmatic
episode the individual may progress to a condition known
as status asthmaticus. This is defined as a severe asthmatic
episode that does not respond to pharmacological control.
Acute airway inflammation causes bronchospasm to worsen.
Mucus plugging, oedema and cellular infiltration lead to
further airway narrowing. Partial obstruction leads to
segmental hyperinflation, which may become extreme and
compromise effective tidal volume. Expiratory flow rates
such as FEV1 and peak flow are also markedly reduced.
If status asthmaticus continues, hypoxaemia worsens,
expiratory flows and volumes decrease further, and effective
ventilation decreases. Metabolic acidosis may accompany
status asthmaticus as the carbon dioxide level in the blood
begins to rise. Asthma becomes a life-threatening condition
at this point, often with impending respiratory or cardiac
arrest if treatment does not reverse this process quickly. A
silent chest (no audible air movement) and a carbon dioxide
level over 70 mmHg are ominous signs of impending death.

E VA LUAT I O N A N D T R E AT M E N T
The diagnosis and monitoring of asthma is undertaken
using spirometry. Spirometry measures lung function and

TABLE 25.2 Common spirometric indices

SPIROMETRIC INDICES

FEV1 — Forced expiratory volume in one second: the volume
of air expired in the first second of the blow volume exhaled

FVC — Forced vital capacity: the total volume of air that can
be forcibly exhaled in one breath

FEV1/FVC ratio — The fraction of air exhaled in the first second
relative to the total

VC — Vital capacity: a volume of a full breath exhaled in the
patient’s own time and not forced. Often slightly greater than
the FVC, particularly in COPD

PEF — The maximum rate of air flow out of the lungs during
forced expiration

Fl
ow

(
L/

Volume (L)

Normal Obstructive–reversible Obstructive–non-reversible
10

8
6
4
2

0
1 2 3 4 5

Fl
ow
(
L/
s)
Volume (L)
10
8
6
4
2
0
1 2 3 4 5
Fl
ow
(
L/
s)
Volume (L)
10
8
6
4
2
0
1 2 3 4 5

A B C

FIGURE 25.5

Flow volume curves.
A Normal. B Obstructive, responsive to bronchodilator treatment. C Obstructive, non-responsive to bronchodilator treatment.
The defining characteristic in obstructive lung disease is a reduction in FEV1 with a normal forced vital capacity (FVC). In B & C, the FVC in
both cases was identical yet FEV1was reduced. The FEV1/ FVC ratio was therefore below the normal 0.7 in healthy individuals. Note the
improvement in B after bronchodilator treatment. These expiratory flow volume curves show pre- and post-bronchodilator spirometry.
The pre-bronchodilator effort is represented by the blue curve and the post-bronchodilator effort by the red curve.

718 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

supported by other clinical signs and symptoms, which
may include but are not limited to a history of allergies
and recurrent episodes of breathlessness or exercise
intolerance. For ongoing asthma management, written
asthma action plans, self-monitoring through peak expiratory
flow monitoring or symptom diaries, self-management
education including disease knowledge and skills (inhaler
technique, adherence) and regular review are essential and
lead to improved health outcomes. A written asthma action
plan (Fig. 25.6) is a set of written instructions that helps
people with asthma detect early signs and symptoms of an
exacerbation and provides instructions about how to manage
these exacerbations. The plan should include instructions
for maintenance therapy, early exacerbation management
and crisis management.5

The goals of long-term asthma management are to achieve
and maintain asthma control, to maintain lung function
and activity, and to prevent morbidity and mortality from
asthma. A stepwise approach is recommended, involving
education, avoidance of triggers and pharmacotherapy
stepped up and down according to asthma control. The
cornerstone of effective asthma management involves
pharmacotherapies including, but not limited to, inhaled
corticosteroids and bronchodilator therapy.5 Medications
are often referred to according to their mechanistic
role:
• Reliever medications: these provide acute relief of

symptoms by allowing rapid bronchodilation. They
relax bronchial smooth muscle and are administered
on an as-needed basis. Examples include salbutamol
or terbutaline (short-acting β2[beta]-agonist) and
ipratropium bromide (anti-muscarinic antagonist).

• Symptom controllers: these provide long-acting
bronchodilation (up to 12 hours) and are administered
twice daily to decrease the symptoms of asthma. These
medications should not be taken to provide rapid relief
of symptomatic asthma. Examples include salmeterol
and eformoterol, both long-acting β2-agonist drugs.

• Preventer medications: these preventative medications
treat inflammation and help achieve overall asthma
control. When the appropriate level has been achieved,
they provide substantial benefits to individuals with
asthma. Examples include inhaled corticosteroids
(beclomethasone dipropionate, budesonide, ciclesonide,
fluticasone propionate, fluticasone furoate), leukotriene-
receptor antagonists (montelukast) and cromones
(cromoglycate and nedocromil).5

There are also combination medications that contain a
symptom controller and preventer medication, enabling
the individual to administer medication in a single inhaler.
Examples include fluticasone and salmeterol (Seretide),
budesonide and eformoterol (Symbicort), fluticasone furoate
and vilanterol (Breo) and fluticasone propionate and
formoterol (Flutiform).

More recently, the use of monoclonal antibody therapies
have been introduced for people with severe asthma.
Anti-immunoglobulin therapy has shown promise in some

people with asthma. Omalizumab is an anti-immunoglobulin
E (IgE) antibody that binds to free IgE and is effective in
combination with other medications in severe persistent
allergic asthma.16 Those who are symptomatic, despite being
managed on high doses of inhaled and oral corticosteroids
or long-acting β2-agonists, and who have failed to respond
to other asthma therapies are most suitable.16 Mepolizumab
is another newer medication, which is an antibody (IgG1,
kappa), that targets human IL-5. IL-5 is the major cytokine
responsible for the growth and differentiation, recruitment,
activation and survival of eosinophils. In some people with
severe asthma it has been shown to significantly reduce
acute exacerbations. Those most likely to respond to
mepolizumab are adults and adolescents with severe asthma,
who experience persistent asthma exacerbations despite
optimal inhaled therapy, and with evidence of high
eosinophil levels from blood counts or sputum.19

There are a growing number of options for management
of chronic asthma depending on the duration of the
condition and the severity of the symptoms, as well as
individual adherence issues. Guidelines have been outlined
and widely distributed by the National Asthma Council
Australia (www.nationalasthma.org.au) and the New Zealand
Guidelines Group (www.nzgg.org.nz). The most important
element of regular asthma management is the reduction
of inflammation.

Acute asthma episodes can be life threatening and
therapy should be directed at maintaining a patent (open)
airway and providing rapid bronchodilation and effective
ventilation to maintain adequate gas exchange (see Table
25.1 for details of the severity of asthmatic episodes).
Administration of oxygen and rapid-acting bronchodilators
such as salbutamol (β2-agonist — that is, one that will
interact with a group of adrenergic receptors in the lungs;
see Chapter 6) are typically used for management of
acute asthma, as well as systemic steroids for moderate to
severe attacks to decrease inflammatory responses in the
lungs.

R E S E A R C H I N F C U S
Asthma genes
Genomic screening of populations suggests that there is no
single ‘asthma gene’ but rather numerous genes that may
be associated with asthma. It may ultimately be possible to
associate certain gene variants with specific clinical patterns
of asthma and with responsiveness to specific asthma
treatments. For example, one variant (or polymorphism) is
the gene for the β2-adrenergic receptor, which has been
shown to be associated with a poor or even adverse response
to salbutamol in one study. If findings such as these can be
corroborated and expanded in larger studies, ultimately it
may be possible to develop individual profiles to optimise
asthma therapy.

http://www.nationalasthma.org.au/

http://www.nzgg.org.nz/

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 719

FIGURE 25.6

Example of an asthma action plan template.
This template plans out the preventer and reliever medications for the patient to use between varying symptoms (from well to worse).

720 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

F O C U S O N L E A R N I N G

1 Discuss the mechanisms that cause obstruction in asthma.

2 Describe the differences in airflow with respect to FEV1 and
FVC during asthma.

3 Discuss the clinical manifestations of asthma in childhood.

4 Explain the full progression of blood gas abnormalities in a
severe asthma episode.

5 Discuss therapy options for individuals with asthma.

P
A

E
D

IA
T

R
IC

Paediatrics and asthma
Asthma affects approximately 10% of children aged 0–14
years in Australia and New Zealand and although the
childhood prevalence of asthma in this region is
decreasing it is still among the highest in the world.5
Unlike asthma prevalence in adults where the rates of
asthma are higher among Indigenous populations
compared with non-Indigenous populations, asthma rates
among these two populations of children are similar.4,5
However, the incidence of severe asthma episodes and
the rate of hospitalisations are greater in Indigenous
populations compared with non-Indigenous populations.4,5

While the pathophysiology of asthma in children is similar
to that of adults, several pertinent points need to be
highlighted. Asthma is clinically different in children due
to the pattern of asthma, natural history and anatomical
features.20 For instance, wheezing in childhood can be
both associated and not associated with asthma. The
classification of asthma is based on the clinical patterns,
rather than objective evaluation using spirometry. There
are currently many theories regarding the mechanisms
of the disease in childhood. There is not one single
gene responsible for the manifestation of asthma. The
wide spectrum of clinical disease probably reflects a
complex interaction between genetic susceptibility
and environmental factors, including early exposure to
allergens and infections, particularly viral respiratory
infections (see ‘Research in Focus: Asthma genes’).
Although the genetic expression of asthma is difficult
to identify, many discrete clinical presentations have
been demonstrated.21 There are at least three different
manifestations for childhood asthma. These are:
1 Transient wheezing limited to the first 3–5 years of

life. This is associated with decreased lung function,
maternal smoking during pregnancy and exposure to
other siblings or children at day-care centres. There
is no association with a family history of asthma.

2 Non-atopic wheezing associated with lower
respiratory tract illness before 3 years of age.

3 IgE-mediated wheezing associated with classic
asthma; an early risk factor for persistent asthma.

Atopy (an allergic reaction when IgE increases due to
environmental allergens — associated with a strong family

history of allergies) is strongly associated with classical
asthma that persists into adulthood. However, wheezing
illnesses in childhood usually resolved by about 6 years
of age, especially when the wheezing is intermittent.5,12,20
The classification of childhood asthma is divided into
three levels: infrequent intermittent, frequent intermittent
and persistent (see Fig. 25.7). Broadly speaking, these
classifications include the following:
1 Infrequent intermittent asthma: isolated episodes

usually triggered by an upper respiratory tract
infection with episodes more than 6 weeks apart.

2 Frequent intermittent asthma: episodes less than 6
weeks apart but similar to infrequent intermittent
asthma.

3 Persistent asthma (mild, moderate, severe): these
children have symptoms of asthma at least weekly
and experience night waking. They have the greatest
number of hospitalisations and usually have asthma
through to adulthood.

In a typical asthmatic episode, the major complaints are
cough, wheeze and shortness of breath. There may or
may not have been signs of a preceding upper respiratory
infection, such as rhinorrhoea (discharge of nasal mucus,

75% Infrequent intermittent
asthma (75%)

Frequent intermittent
asthma (20%)

Persistent asthma (5%)

20%

FIGURE 25.7

Classification of childhood asthma and their distribution.
Infrequent, intermittent asthma is the most common type of
childhood asthma.

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 721

with systemic consequences including systemic inflammation
and complex chronic comorbidities.28 This results in
significant and progressive functional impairment with
reduced exercise capacity and increased exacerbations.29
(Fig. 25.8).

COPD is diagnosed using spirometry, with a FEV1/FVC
ratio of less 70% following administration of a
bronchodilator.30 The ratio should be greater than 70% in
individuals without airway obstruction lung pathophysiology:

FEV
FVC

or more in healthy airways1 100 70× = %

This is combined with a thorough history including
history of smoking (or exposure to other noxious inhalational
agents).

The disease is primarily caused by cigarette smoke (of
any cigarette type) and both active and passive smoking
have been implicated. This is the most important cause of
COPD, and smokers demonstrate a steady decline in
pulmonary function (see Fig. 25.9). The risk of developing
COPD with continued long-term smoking, irrespective of
cigarette type, is high. Other risks include inhaled noxious
particles such as occupational exposure and air pollution.
In the following sections we take a closer look at the two
main conditions that result in COPD.

CHRONIC BRONCHITIS
Chronic bronchitis is defined as hypersecretion of mucus
and chronic productive cough for at least 3 months of the
year (usually the winter months) for at least 2 consecutive
years.26 It is almost always caused by cigarette smoking and
by exposure to inhaled noxious particles. It differs from
episodes of acute bronchitis, which are usually caused by
infection and are reversible, whereas chronic bronchitis is
an irreversible condition of progressive decline.

PAT H O P HYS I O LO G Y
Inspired irritants result in airway inflammation with
infiltration of neutrophils, macrophages and lymphocytes
into the bronchial wall. Continual bronchial inflammation
causes bronchial oedema and increases the size and

Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) is a
progressive chronic disease characterised by irreversible
obstruction of the airways. It is Australia’s fourth leading
cause of death and third leading cause of disability.22
Moderate to severe COPD affects 7.5% of Australians over
40 years with prevalence rising rapidly with age; 29% of
Australians over 75 years have COPD.23 Worldwide, COPD
is the third leading cause of death.24 An economic report
estimated the cost of COPD in Australia as $8 billion.25
This consisted of lost productivity ($6.8 billion), health
system expenditure ($0.9 billion), patient expenses ($0.3
billion), and additional COPD-related welfare payments
($0.9 billion). People with COPD experience multiple clinical
management problems related to airway, comorbidity, risk
factors and self-management domains, and these problems
have a major impact on health status.

COPD is a preventable, chronic disease that is
characterised by persistent respiratory symptoms and airflow
limitation, which is due to airway or alveolar abnormalities,
that are usually caused by significant exposure to noxious
particles or gases, with the most common cause being
cigarette smoking.26 The airflow limitation in COPD is largely
irreversible. COPD can be characterised pathophysiologically
by emphysema, chronic bronchitis (and bronchiolitis), or
commonly the coexistence of both emphysema and chronic
bronchitis. The airflow limitation is caused by damage
to the small airways, as a result of two main diseases:
chronic bronchitis, which consists of airway inflammation
and remodelling, and emphysema, which consists of
destruction of alveolar tissue, and a decrease in elastic
recoil.26

COPD is associated with a range of immunological
processes. In COPD neutrophils, macrophages and CD8+
T-lymphocytes play a major role in the airway inflammation
and lung damage. Proinflammatory cytokines such as IL-6,
IL-8, IL-1β and tumour necrosis factor alpha (TNF-α) are
also released in the COPD airway. Eosinophilic airway
inflammation occurs in approximately 30% of individuals
with the disease.27

While COPD is primarily a pulmonary condition, it is
now also recognised as a multi-system disease associated

often termed ‘runny’ nose) or low-grade fever. In children,
about 70–80% of acute wheezing episodes are associated
with viral respiratory infections. In infants and toddlers
under 2 years old, the most common of these is respiratory
syncytial virus. In older children and adults, the major
viral trigger is rhinovirus (commonly referred to as the
‘common cold’ virus).
On physical examination, there is an expiratory wheeze
that is often described as high-pitched and musical, and
exhalation is unusually longer than inhalation. Breath

sounds may become faint when air movement is poor. The
child may speak in short sentences or not at all because of
dyspnoea (difficulty breathing). Ventilatory rate and heart
rate are elevated to compensate for the low oxygen levels
and increased work of breathing. Nasal flaring and use
of accessory muscles with retractions in the substernal,
subcostal, intercostal, suprasternal or sternocleidomastoid
muscle areas are evident. The child may appear anxious
or be diaphoretic (excessive sweating), which are often
important signs of respiratory compromise.

722 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

number of mucous glands and goblet cells in the airway
epithelium. Thick, tenacious mucus is produced and cannot
be cleared because of impaired ciliary function. The defence
mechanisms of the pulmonary system are compromised,
increasing susceptibility to pulmonary infection and
injury. Frequent infectious exacerbations are complicated
by bronchospasm with dyspnoea and a productive cough.
The pathophysiology of chronic bronchitis is shown in
Fig. 25.10.

Initially this process affects only the larger bronchi, but
eventually all airways are involved. As the airways become
increasingly narrowed, airway obstruction results (see Figs
25.11 and 25.12). The airways collapse early in expiration,
trapping gas in the distal portions of the lung. Eventually
ventilation–perfusion mismatching (see Chapter 24) and
hypoxaemia occurs. Extensive air trapping puts the
respiratory muscles at a mechanical disadvantage, resulting
in hypoventilation and hypercapnia.

Cigarette
smoke

Spill-over

SYSTEMIC INFLAMMATION
Cytokines, IL-1�, IL-6, IL-18, TNF�
Acute phase proteins: CRP

Peripheral lung
inflammation

Biomass
fuel

Normal ageing

Physical activity

Skeletal muscle
weakness
Cachexia

Cardiovascular
– Coronary artery disease
– Chronic heart failure
– Hypertension

Metabolic diseases
– Diabetes
– Metabolic syndrome
– Obesity

Bone disease
Osteoporosis
Osteopenia

Depression

Hypoxia

FIGURE 25.8

COPD, systemic inflammation and comorbidities.
Chronic inhalation of smoke leads to COPD and lung inflammation, which can lead to systemic inflammation. COPD also leads to a
reduction in physical activity, which worsens systemic inflammation. The consequences of this chronic systemic inflammation can include
cardiovascular, metabolic, and bone disorders, as well as depression.

R E S E A R C H I N F C U S
Coexisting asthma and COPD
Asthma and COPD are most often considered distinct
conditions with different diagnostic and management
approaches. However, in practice, patients frequently exhibit
features of more than one disease particularly in an older
population. This is referred to as asthma-COPD overlap and
refers to the coexistence of asthma, emphysema or chronic
bronchitis; it is prevalent in over 50% of people over the age
of 50 years, and people who have features of both diseases
experience more frequent and severe exacerbations, increased
symptom burden and worse health status. Traditionally people
with features of both diseases have been excluded from
clinical trials, and as a result the evidence base for
management of asthma-COPD overlap is limited. This area
is currently a focus of research.

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 723

workload of breathing, so that late in the course of
disease, many individuals will develop hypoventilation and
hypercapnia.

C L I N I C A L MA N I F E S TAT I O N S O F CO P D
Table 25.3 lists the common clinical manifestations of COPD
including chronic bronchitis.

Acute exacerbations of COPD are a common feature
which put the patient at immediate risk of distress,
hospitalisation and even death. Acute exacerbations represent
a significant contribution to the healthcare costs associated
with these conditions.31

Acute exacerbations of COPD are not only a concern
during the immediate time of that exacerbation; after
recovery they can also have a negative effect on disease
trajectory. In COPD the frequency of exacerbations is
associated with an accelerated decline in lung function,
accelerated decrease in health status and decreased survival
(Fig. 25.14). Furthermore, recent evidence indicates that
exacerbations cluster together in time and that after
one exacerbation patients are at a heightened risk of a
second.32 This is important given the detrimental effect
recurrent exacerbations have on outcomes for people with
COPD.

E VA LUAT I O N A N D MA N AG E M E N T O F CO P D
Under-diagnosis of COPD is common; rates of
under-diagnosis have been reported as high as 78%.33
Disease-specific guidelines propose diagnostic criteria to
assist clinicians in the diagnosis of COPD. In clinical
practice, COPD is usually diagnosed based on a history of
smoking, or exposure to other noxious agents and a FEV1/
FVC% (otherwise known as forced expiratory ratio (FER))
of less than 70%.30 The Australian and New Zealand
guidelines for treatment are based on the spirometry severity
grading scale.30 Other useful assessments in the evaluation
include pulmonary function tests to measure lung volumes
and gas diffusion, chest x-rays, blood gas analysis and
physical examination.

The goals of COPD management are to reduce the risk
of exacerbation and minimise symptoms.30 This approach
recommends short-acting bronchodilators and reduction
of risk by stopping smoking, and by ensuring influenza
vaccinations across all COPD severity grades. Addition-
ally, pharmacotherapy including inhaled glucocorticos-
teroids and long-term oxygen therapy is recommended
as severity, symptoms and exacerbation frequency
increase. Pulmonary rehabilitation is recommended for
COPD individuals who are symptomatic regardless of
severity.30,34

CYSTIC FIBROSIS
Cystic fibrosis is the most common autosomal recessive
inherited disease affecting Caucasians and results from
defective epithelial chloride ion transport. The chromosomal
mutation results in the abnormal expression of the protein,
cystic fibrosis transmembrane conductance regulator, which
is a chloride channel (it allows the diffusion of chloride

EMPHYSEMA
Emphysema is abnormal permanent enlargement of
gas-exchange airways accompanied by destruction of alveolar
walls. Obstruction results from changes in lung tissues,
rather than mucus production and inflammation as in
chronic bronchitis. The major mechanism of airflow
limitation is loss of elastic recoil (see Fig. 25.11). The major
cause of emphysema is cigarette smoking, although air
pollution and childhood respiratory infections are
contributing factors.

PAT H O P HYS I O LO G Y
Emphysema begins with destruction of alveolar septa, which
eliminates portions of the pulmonary capillary bed and
increases the volume of air in the alveoli (see Fig. 25.13).
It is postulated that inhaled oxidants in tobacco smoke and
air pollution stimulate inflammation, which over time
causes alveolar destruction and loss of the normal elastic
recoil of the bronchi (see Fig. 25.10). Alveolar destruction
produces large air spaces within the lung tissue and air
spaces adjacent to pleurae. These areas are not effective in
gas exchange. The loss of alveolar tissue means a loss of
the respiratory membrane where gases cross between air
and the blood, resulting in a significant ventilation–
perfusion mismatching and hypoxaemia. Expiration
becomes difficult because loss of elastic recoil reduces the
volume of air that can be expired passively and air is
trapped in the lungs. Air trapping causes an increase in
expansion of the chest, which puts the muscles of ventilation
at a mechanical disadvantage. This results in increased

Smoked regularly
and susceptible to
the effects

100

Age (years)
25 50 75

(%
o

f v
al

ue
a

t a
ge

2
5
y

ea
rs

)

Onset of symptoms

Death

Severe disability

Stopped smoking
at age 65 years

Never smoked or not
susceptible to smoke

Stopped smoking
at age 45 years

FIGURE 25.9

Time course of smoking and the changes with smoking
cessation at 45 and 65 years of age.
Notice that for the smoker who quit at age 45, the serious
progression of COPD is much slower than that for the smoker who
quit at age 65. In both cases, the disease progression is slower
than for those who continue smoking.

724 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe
C

O
N

C
E

P
T

M
A

P Tobacco smokeAir pollution

Inflammation of the
airway epithelium

Systemic effects
(muscle weakness, weight loss)

Breakdown in
lung elastic tissue

causes
causes
leads to
leads to

results in results in

can result in

evidenced by

Continuous bronchial
irritation and inflammation

Chronic bronchitis
(bronchial oedema, hypersecretion of

mucus, bacterial colonisation of airways)

Emphysema
(destruction of alveolar septa and

loss of elastic recoil of bronchial walls)

Infiltration of inflammatory
cells and release of cytokines
(neutrophils, macrophages,
lymphocytes, leukotrienes,

interleukins)

Airway obstruction
Air trapping

Loss of surface area for gas exchange
Frequent exacerbations

(infections, bronchospasm)

Dyspnoea
Cough

Hypoxaemia

Hypercapnia

Cor pulmonale

FIGURE 25.10

The pathophysiology of COPD.
Chronic inhalation of smoke leads to inflammation of the lungs. This inflammation manifests as bronchial inflammation and mucus
production, leading to chronic bronchitis, and also manifests as break down of alveolar tissue, leading to emphysema. Together,
chronic bronchitis and emphysema lead to significant impairments in breathing, leading to symptoms that may be severe for the
patient.

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 725

respiratory failure and death.36 The typical features of
cystic fibrosis lung disease are mucus plugging, chronic
inflammation and chronic infection. The mucus plugging
seen in cystic fibrosis probably results from both increased
production of mucus and altered chemical properties of
the mucus. Mucus-secreting airway cells (goblet cells
and submucosal glands) are increased in number and
size. Cystic fibrosis mucus is dehydrated and viscous
because of defective chloride secretion and excess sodium
absorption — as a result, the mucus secretions are thick
and sticky. This decreases the fluid volume on the airway
surface, impairing the mobility of the cilia and thereby
allowing mucus to adhere to the airway epithelium,
along with bacteria and injurious byproducts from
neutrophils.

Chronic inflammation is believed to contribute to
long-term lung damage and there is evidence that this

out of the cell) present on the surface of many types of
epithelial cells including the airways, bile ducts, pancreas,
sweat ducts and vas deferens.

In Australia, approximately 1 in 3630 people are born
with cystic fibrosis, and about 1 in 25 are carriers who
are not affected by the mutation.35 Cystic fibrosis has long
been considered a disease of childhood; however, over
time there have been significant improvements in the
management and treatment options for people with cystic
fibrosis, such that in the last four decades the survival has
improved dramatically. Improved treatments and increased
survival have consequently led to a significant increase in
the number of adult patients with cystic fibrosis, such that
cystic fibrosis can no longer be considered a paediatric
disease alone. The number of cystic fibrosis patients over
the age of 18 has increased significantly and the most
recently published data from the Australian cystic fibrosis
data register report that approximately half of patients
are adults.35

PAT H O P HYS I O LO G Y
Although cystic fibrosis affects many organs (endocrine,
gastrointestinal, renal and reproductive systems) the
most important effects are on the lungs and in 90% of
cases, chronic pulmonary infections eventually lead to

Muscle

Air movement
during INSPIRATION

Air movement
during EXPIRATION

Mucus
plug

Bronchial
walls
collapse

Alveolar walls

FIGURE 25.11

Mechanisms of air trapping in chronic obstructive pulmonary
disease.
During inspiration, the force of airflow is sufficient to overcome
the mucus. However, during expiration, the airways partially
collapse, and the mucus becomes sufficient to plug the airway to
a much greater extent, causing difficulty exhaling.

Pulmonary artery
Cartilage Submucosal
gland
Basement
membrane
Epithelium
Goblet cell
Alveoli
Mucus
accumulation
Mucus
plug
Hyperinflation
of alveoli
Respiratory
bronchioles
Bronchioles
Mast cell
Parasympathetic
nerve
Smooth
muscle

Enlarged
submucosal
gland

Inflammation
of epithelium

A
B

FIGURE 25.12

Airway obstruction resulting from chronic bronchitis.
A Normal lungs with clear airways. B Inflammation and airway
thickening of mucous membrane with accumulation of mucus and
pus leading to obstruction and characterised by a cough.

726 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

the age of 30 years.37 Combined with chronic bacterial
infection, these lead to microabscess formation,
bronchiectasis, patchy consolidation and pneumonia,
peribronchial fibrosis and cyst formation (see Fig. 25.15).
There is a progressive decrease in the amount of available
and functional lung tissue. The pathophysiology for these
changes are outlined in Fig. 25.16. Over time, pulmonary

process begins in infancy. Abnormal cytokine profiles
promote a proinflammatory state.

Individuals with cystic fibrosis have a propensity for
chronic bronchial infection. It is likely that local factors in
the cystic fibrosis airway microenvironment favour bacterial
colonisation, because there is no systemic immune defect.
Staphylococcus aureus and Pseudomonas aeruginosa are
common, and Pseudomonas aeruginosa ultimately colonises
airways in approximately 70% of adults between the ages
of 18 and 29 and 82.3% of adults with cystic fibrosis over

A B

FIGURE 25.13

The effects of emphysema on the gas exchange units.
A Normal lung with many small alveoli. B Lung tissue affected by emphysema. Notice that the alveoli have merged into larger air spaces,
reducing the surface area for gas exchange.

TABLE 25.3 Clinical manifestations of COPD

VARIABLES BRONCHITIS EMPHYSEMA

Age (years) 40–45 50–75

Infections Common Occasional

Dyspnoea Mild, late in
course

Severe, early in
course

Productive cough Classical sign Late in course with
infection

Wheezing Intermittent Common

History of smoking Common Common

Prolonged
expiration

Always present Always present

Cyanosis Common Uncommon

Chronic
hypoventilation

Common Late in course

Chest x-ray
findings

Prominent vessels Hyperinflation

General
appearance

‘Blue bloater’ ‘Pink puffer’

Barrel chest Occasionally Classic

Exacerbation
Q

ua
lit

y
of

li
fe

Death
Time

Progressive
decline in
lung function

Decline in quality
of life with
exacerbations

FIGURE 25.14

Effect of exacerbations on lung function and quality of life in
COPD.
In the individual with COPD, there is a progressive decline in lung
function. However, exacerbations can cause the decline to
progress quicker, leading to a quicker decline in the quality of life.

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 727

(meconium blocking the bowel) at birth, which is indicative
of cystic fibrosis. Approximately 80% of individuals with
CF have pancreatic insufficiency leading to malabsorption,
symptoms include frequent, loose and oily stools and, if
not treated, either meconium ileus in infants or distal
intestinal obstructive syndrome in adults develops. More
subtle presentations include chronic sinusitis, nasal polyps
and rectal prolapse. Complications of cystic fibrosis may
include liver disease and cystic fibrosis related diabetes,
each of which occurs in approximately one-quarter
of adults.

E VA LUAT I O N A N D T R E AT M E N T
In Australia and New Zealand, newborn infants are screened
for cystic fibrosis. The blood test measures pancreatic enzyme
levels and, if the levels are abnormal, genetic testing for
the cystic fibrosis mutation is undertaken. However, the
testing is not definitive: there are numerous cystic
fibrosis-associated mutations and up to 5% of all tests will
not be conclusive. Therefore, the definitive diagnosis is
confirmed from a sweat test, which determines the level

vascular remodelling occurs because of localised hypoxia
and arteriolar vasoconstriction, and pulmonary hypertension
and cor pulmonale (right ventricular enlargement) may
develop in the late stages of disease.

C L I N I C A L MA N I F E S TAT I O N S
The most common presentations are respiratory or
gastrointestinal. Respiratory symptoms include persistent
cough or dyspnoea and recurrent or severe pulmonary
infection. Lung function decreases in individuals with
cystic fibrosis with increasing age. For instance, at 18 years,
FEV1 is approximately 80% of predicted volumes.37 Physical
signs that develop over time include barrel chest and digital
clubbing. Over time, more serious pulmonary conditions
may arise, such as haemoptysis and pneumothorax (see
‘Clinical manifestations of pulmonary alterations’). Classic
gastrointestinal presentations include meconium ileus

R E S E A R C H I N F C U S
Nutrition and COPD
Malnutrition is a major concern for individuals with COPD
because they have increased energy expenditure, decreased
energy intake and impaired oxygenation. The disproportionate
muscle wasting is similar to that which occurs with other
chronic diseases, such as cancer, heart failure and AIDS.
Systemic inflammatory mediators may impair appetite and
contribute to hypermetabolism. There are several detrimental
effects of malnutrition: (1) adversely affects exercise tolerance
by limiting skeletal and respiratory muscle strength and
aerobic capacity; (2) limits surfactant production; (3) reduces
cell-mediated immune responses; (4) reduces production
of proteins (protein synthesis); and (5) increases morbidity
and mortality. The goal of medical nutrition therapy is to
maintain an acceptable and stable weight for the individual.
This can be accomplished by including foods of high energy
density, snacking frequently, choosing soft foods, having an
adequate intake of fluids and providing assistance with
shopping and meal preparation. Increasing omega-3 fatty
acids and antioxidant intake may modulate the effects of
systemic inflammation. Protein intake should be maintained
at 1.0–1.5 g/kg of body weight, and a daily vitamin C
supplement should be added to the diet if the individual is
still smoking.

On the other hand, obesity is observed at high rates of
prevalence in COPD, and the prevalence is increasing. The
rates of obesity in COPD have been reported at rates with
an even higher prevalence than that seen in the general
population. Obesity is usually associated with increased risk
of all cause mortality in the general population, and is linked
to metabolic syndrome. Discordantly, obesity in COPD is
associated with improved survival and reduced lung function
decline. The focus of current research is to define the best
approach to the management of obesity in COPD populations.

FIGURE 25.15

The pathology of the lung in cystic fibrosis.
Key features are widespread mucus impaction of airways and
bronchiectasis (especially from upper lobe [U]), with haemorrhagic
pneumonia in the lower lobe (L). Small cysts (C) are present at the
apex of the lung.

728 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

of sweat chloride concentration (indicative when in excess
of 60 mmol/L).

Treatment is primarily focused on pulmonary health and
nutrition. Common pulmonary therapies include techniques
to promote mucus clearance, such as chest physical therapy
and positive pressure devices, bronchodilators, aerosolised
DNase which liquefies mucus, and inhaled mucolytics such
as hypertonic saline and mannitol. Inhaled maintenance
antibiotics can be used to suppress Pseudomonas aeruginosa
when it is present and this has a beneficial clinical impact.
Oral antibiotics are used fairly liberally for minor pulmonary
exacerbations. Intravenous antibiotics are used to treat
more severe exacerbations of pulmonary infection. Lung
transplantation is an option for selected individuals with
end-stage lung disease from cystic fibrosis. Complications
are usually related to infection or rejection and survival at
5 years posttransplant is approximately 67%.38

Approximately 80% of individuals with cystic fibrosis
have pancreatic insufficiency and therefore need to take

pancreatic enzymes (for digestion of nutrients) before meals
and snacks for their entire lifetime. Fat-soluble vitamins
must be supplemented. Energy needs are high, especially
with advancing lung disease and high-kilojoule supplements
or even gastrostomy feeding may be warranted. Nutritional
care for individuals with cystic fibrosis has become
increasingly aggressive because of the documented link to
better long-term outcomes.

Fortunately, there have been major improvements in
cystic fibrosis outcomes over the last few decades. These
improvements are related to advances in treatment but of
equal importance relate to the specialist multidisciplinary
centres for children and adults with cystic fibrosis. Specialist
centre care has been shown to be associated with improved
clinical outcomes for children and adults; those treated in
these centres have better nutritional status, chest x-ray scores
and pulmonary function compared to other cystic fibrosis
patients, and this approach is recommended as an essential
component of management.

C
O
N
C
E
P
T
M

A
P Chromosome 7CFTR defect

Defective
chloride secretion

Cilia
movement

Mucus plugs and
impaired mucus clearance

Pulmonary
defence mechanisms

Chronic bacterial
infection

Chronic
in�ammation

Cyst
formation

Bronchiectasis

Dehydrated
mucus

Viscous
mucus

causes

leads toimpairs

affects

results in

results in
(over time)

leads to
leads to

contributes to contributes tocontributes to

FIGURE 25.16

The pathogenesis of bronchiectasis and cyst formation in cystic fibrosis.
The altered chloride secretion leads to dehydrated, thick mucus, which cannot be moved easily by the impaired cilia. As a result,
mucus accumulates and impairs normal pulmonary defence mechanisms, leading to infections and inflammation. CFTR = cystic
fibrosis transmembrane regulator.

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 729

R E S E A R C H I N F C U S
New treatments for cystic fibrosis
There have been recent advances in cystic fibrosis with the
development of new therapies that target specific defects
of the CFTR (cystic fibrosis transmembrane conductance
regulator) function. The first CFTR modulator approved for
use in cystic fibrosis is Ivacaftor. Ivacaftor targets the
underlying protein defect in patients with the G551D
mutation, and has been show to significantly improve lung
function, exacerbations rates, weight and quality of life in
adults. Lumacaftor/Ivacaftor combination is another targeted
therapy that leads to improved lung function, exacerbations
and nutrition in a subset of patients with cystic fibrosis. These
treatments represent a new era of precision medicine in
cystic fibrosis and emerging therapies are currently being
developed and trialled.

FIGURE 25.17

Bronchiectasis on a chest x-ray.
Note the dilated bronchi close to the midline (see arrows).

Bronchiectasis is a debilitating illness in which individuals
suffer significant respiratory morbidity and poor
health-related quality of life. Exacerbations occur at rates
of 1.5–6.5 per patient per year and are associated with an
increased risk of admission and readmission to hospital,
and high healthcare costs.39 Data estimating rates of hospital
admissions, average length of stay and the economic burden
of the disease give an indication as to the impact of this
condition. The average annual age-adjusted rate of
hospitalisations is 16.5 per 100 000 population,40 and an
average annual increase of hospitalisation rates of 2.4%
among men and 3.0% among women was identified between
1993 and 2006. These data highlight the need to optimise
management of the disease. It is increasingly recognised
that bronchiectasis may coexist with other common
respiratory diseases such as COPD and asthma and that
many of the clinical consequences may overlap. Literature
reports up to 57% of people with COPD have coexisting
bronchiectasis41 and 24.8% of people with severe persistent
asthma have been shown to have coexisting bronchiectasis
when examined with high resolution CT scan, despite being
previously undiagnosed.42

Bronchiectasis is associated with multiple comorbidities
that may alter the disease presentation, be a systemic
consequence of the same pathophysiological process or act
as confounding factors in the diagnosis and treatment of
the disease.

The symptoms of bronchiectasis may date back to a
childhood illness or infection. The disease is commonly
associated with recurrent lower respiratory tract infections
and expectoration of large amounts of purulent sputum
and haemoptysis are common. Pulmonary function studies
show decreased vital capacity and expiratory flow rates.
Bronchiectasis is often associated with bronchitis and
atelectasis. Treatment of bronchiectasis involves avoidance
and management of chest infections, antibiotics, airway
clearance techniques, mucolytic agents and pulmonary
rehabilitation in individuals who experience dyspnoea as
part of their activities of daily living.

BRONCHIECTASIS
Bronchiectasis is an abnormal permanent dilation and
distortion of the bronchi and bronchioles, resulting from
chronic inflammation of the airways, and leading to
progressive destruction of the bronchial walls and lung
tissue. Bronchiectasis has a distinctive appearance on x-rays
(see Fig. 25.17) and chest computerised tomography (CT)
scans.

The prevalence of bronchiectasis among adults in
Australia and New Zealand is largely uncertain due to lack
of population studies and it is likely that any existing
bronchiectasis prevalence rates are underestimated due to
lack of diagnosis or misdiagnosis of the disease.

F O C U S O N L E A R N I N G

1 Differentiate between the different components of COPD.

2 Discuss the anatomical and pathophysiological changes in
chronic bronchitis.

3 Describe the changes in oxygenation and ventilation in
individuals with emphysema.

4 Describe the pathogenesis of impaired mucus clearance
and lung changes in cystic fibrosis.

Restrictive airway diseases
Restrictive airway diseases are not as prevalent as obstructive
airway diseases in the Australian and New Zealand
populations. They are fundamentally different from
obstructive diseases, but many of the clinical manifestations

730 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

are similar. Therefore, it is essential that you can differentiate
between these two groups of disorders, such that clinical
management can be directed appropriately.

Restrictive lung diseases are characterised by decreased
compliance (stretchiness) of the lung tissue, resulting in
an increased work of breathing. Individuals with lung
restriction complain of dyspnoea and have an increased
ventilatory rate and decreased tidal volume — that is, they
breathe fast but with smaller breath size. Pulmonary function
testing reveals a decrease in FVC often accompanied with
a reduction in FEV1. Therefore, the ratio of FEV1/FVC can
be normal but usually increased — that is, about 80% of
the forced expired air is expelled from the lungs in the first
second — yet the overall amount of air forcibly exhaled is
less than normal (see Fig. 25.18). Restrictive lung diseases
commonly affect the alveolar–capillary membrane and cause
decreased diffusion of oxygen from the alveoli into the
blood, resulting in hypoxaemia. Some of the most common
restrictive lung diseases in adults are acute respiratory
distress syndrome, inhalational disorders, idiopathic
pulmonary fibrosis and interstitial lung disease.

Acute respiratory distress syndrome
Acute respiratory distress syndrome is a dramatic
life-threatening condition characterised by acute lung
inflammation and diffuse alveolar capillary injury. It can
affect all age groups. Individuals who progress to acute

Fl
ow
(
L/
s)
8
6
4
2
0
Volume (L)

FIGURE 25.18

Flow volume loop — restrictive lung disease.
These expiratory flow volume curves show pre- and post-
bronchodilator spirometry. The pre-bronchodilator effort is
represented by the blue curve and the post-bronchodilator effort
by the red curve. Note that there is a reduction in both FEV1 and
FVC. Therefore, when calculated, the FEV1/FVC ratio is not
different from that in healthy individuals; however, there is
restriction throughout the entire expiratory phase.

respiratory distress syndrome typically are critically ill and
require intensive care treatment. The mortality rate is high;
however, advances in therapy have decreased mortality in
people younger than 60 years. The most common
predisposing factors are sepsis and multiple trauma; however,
there are many other causes, including pneumonia, burns,
aspiration, cardiopulmonary bypass surgery, pancreatitis,
blood transfusions, drug overdose, high concentrations of
supplemental oxygen and disseminated intravascular
coagulation.

PAT H O P HYS I O LO G Y
The hallmark of acute respiratory distress syndrome is lung
inflammation. There is activation of the inflammatory
response (see Fig. 25.19), including complement, cytokines,
arachidonic acid metabolites and platelet-activating factor.

All disorders causing acute respiratory distress syndrome
cause massive pulmonary inflammation that injures the
alveolar–capillary membrane and which produces severe
pulmonary oedema and hypoxaemia. The damage can occur
directly, as with the aspiration of highly acidic gastric
contents or the inhalation of toxic gases, or indirectly from
chemical mediators released in response to systemic
disorders such as sepsis. Injury to the pulmonary capillary
endothelium stimulates platelet aggregation (platelets
sticking together) and intravascular thrombus formation.
Endothelial damage also initiates the complement cascade,
stimulating neutrophil and macrophage activity and the
inflammatory response.

Once activated, macrophages produce toxic mediators
such as tumour necrosis factor-alpha (TNF-α) and
interleukin-1 (IL-1) (see Chapter 12). The role of neutrophils
is central to the development of acute respiratory distress
syndrome. Activated neutrophils release a battery of
inflammatory mediators, including proteolytic enzymes
(enzymes that break down proteins), toxic oxygen products,
arachidonic acid metabolites (prostaglandins, thromboxanes,
leukotrienes) and platelet-activating factor. These mediators
extensively damage the alveolar–capillary membrane and
greatly increase capillary membrane permeability. This
allows fluids, proteins and various blood cells to leak
from the capillary bed into the pulmonary interstitium
and alveoli. The resulting pulmonary oedema severely
reduces lung compliance and impairs alveolar ventilation.
Mediators released by neutrophils and macrophages
also cause pulmonary vasoconstriction, which leads to
worsening of ventilation–perfusion mismatching and
hypoxaemia. This vicious cycle continues and is difficult
to halt.

The initial lung injury also damages the alveolar
epithelium. This cell injury increases alveolar capillary
permeability, increases susceptibility to bacterial infection
and pneumonia, and decreases surfactant production. Alveoli
and respiratory bronchioles fill with fluid or collapse. The
lungs become less compliant, ventilation of alveoli decreases
and pulmonary blood flow is shunted right to left. The
work of breathing increases. The end result is acute
respiratory failure.

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 731
C

O
N
C
E

P
T M

A
P

Neutrophil aggregation and
release of mediators

Alveolar-capillary
membrane permeability

Clinical lung injury

Alveolar epithelial
damage

Type II pneumocyte
damage

Endothelial
damage

Platelet
aggregation

results in

starts

causes

precipitates

increases

allows

results in

contributes to contributes to

leads to

can cause

causes
causes
affects

also

initiates

causescontributes

causes
causes
causes

Release of neutrophil
chemotactic factors

Complement
activation

Bacterial
endotoxin release

Macrophage
mobilisation

Release of
cytokines (TNF, IL-1)

Vasoconstriction

Decreased �ow
to selected areas

Ventilation
perfusion mismatching

Exudation of �uid,
protein, RBCs into

interstitium

Pulmonary oedema
and haemorrhage with

severe impairment
of alveolar ventilation

Acute respiratory failure

Decreased
surfactant production

Bacterial
infection

Atelectasis and
impaired lung
compliance

Pneumonia

Hypoxaemia

FIGURE 25.19

The proposed mechanism for the pathophysiological changes associated with acute respiratory distress syndrome.
Damage to the alveoli leads to increased susceptibility to pneumonia and atelectasis. Damage to endothelial cells leads to activation
of platelets and complement, which triggers a series of events that can result in pulmonary oedema and hypoxaemia. IL-1 = interleukin-1;
RBCs = red blood cells; TNF = tumour necrosis factor.

732 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

disease, the individual’s history of exposure is important
in determining the diagnosis. Pneumoconiosis often occurs
after years of exposure to the offending dust, with progressive
fibrosis of lung tissue. Asbestosis, silicosis and coal worker’s
pneumoconiosis are among the three most important
dust-related diseases from occupational exposure in
Australia, and recent local and international data suggest
that there is a resurgence of coal worker’s pneumoconiosis.43
Asbestosis has the highest mortality of these three; though
the risk of environmental exposure has been recognised
for decades, it is to be hoped that with the controls now
in place, exposure to asbestos will be limited in the future.
However, there is also some concern remaining regarding
exposure to asbestos, due to individuals undertaking their
own home renovations, as the untrained renovator may
disturb asbestos from numerous products that were used
previously in home construction.

Deposition of dusts from silica, asbestos and coal leads
to chronic inflammation. In addition, scarring of the
alveolar–capillary membrane leads to a build-up of
connective tissue in the lung (termed pulmonary fibrosis).
These dust deposits are permanent and lead to progressive
pulmonary deterioration. Clinical manifestations with
advancement of disease include cough, chronic sputum
production, dyspnoea, decreased lung volumes and
hypoxaemia. Diagnosis is confirmed by chest x-ray and CT
scans. Treatment (such as pain control) is usually palliative
(to reduce symptoms of the disease) and focuses on
preventing further exposure, particularly in the workplace.

The chemical mediators responsible for the alveolar
capillary damage of acute respiratory distress syndrome
often cause widespread inflammation, endothelial damage
and capillary permeability throughout the body, resulting
in the systemic inflammatory response syndrome, which
then leads to multiple organ dysfunction syndrome. In fact,
death may not be caused by respiratory failure alone but
by multiple organ dysfunction syndrome associated with
acute respiratory distress syndrome. (Multiple organ
dysfunction syndrome is discussed in Chapter 23.)

C L I N I C A L MA N I F E S TAT I O N S
Acute respiratory distress syndrome develops acutely after
the initial insult, usually within 24 hours, though occasionally
it is delayed up to a few days. The classic signs and symptoms
of acute respiratory distress syndrome are marked dyspnoea,
rapid shallow breathing, inspiratory crackles, respiratory
alkalosis, decreased lung compliance, hypoxaemia
unresponsive to oxygen therapy (called refractory
hypoxaemia) and diffuse alveolar infiltrates seen on chest
x-rays, without evidence of cardiac disease.

E VA LUAT I O N A N D T R E AT M E N T
Diagnosis is based on physical examination, analysis of
blood gases and radiological examination. Treatment for
acute respiratory distress syndrome remains supportive in
nature and the goals are to maintain adequate tissue
oxygenation, minimise acute lung injury and avoid further
pulmonary complications. Most individuals with acute
respiratory distress syndrome require mechanical ventilation
and often relatively high levels of positive end-expiratory
pressure to promote alveolar ventilation and stabilisation
and redistribution of alveolar oedema fluid into the
interstitium.

Inhalation disorders
EXPOSURE TO TOXIC GASES
Inhalation of gaseous irritants can cause significant
respiratory dysfunction. Gases that are toxic to the
pulmonary system include smoke, ammonia, hydrogen
chloride, sulfur dioxide, chlorine and nitrogen dioxide.
Inhalation of a toxic gas results in severe inflammation of
the airways, alveolar and capillary damage and pulmonary
oedema. Initial symptoms include burning of the eyes, nose
and throat; coughing, chest tightness and dyspnoea.
Hypoxaemia is common. Treatment includes supplemental
oxygen, mechanical ventilation and support of the
cardiovascular system due to hypotension. Most individuals
respond quickly to therapy. Some, however, may improve
initially then deteriorate as a result of bronchiectasis
(persistent dilation of the bronchioles) or bronchiolitis
(inflammation of the bronchioles).

PNEUMOCONIOSIS
Pneumoconiosis represents any change in the lung caused
by inhalation of inorganic dust particles, usually in the
workplace. As in all cases of environmentally acquired lung

F O C U S O N L E A R N I N G

1 Describe the pathophysiology of acute respiratory distress
syndrome.

2 Discuss the clinical manifestations of acute respiratory
distress syndrome and how they progress differently from
other lung diseases.

3 Differentiate between inhalational gas and particle
exposure.

Infections of the
pulmonary system
Infections of the pulmonary system are some of the most
common infections in humans. Symptoms of respiratory
infection include increased sputum, cough, sore throat and
fever; mild infections do not usually require medical
intervention. Most of these infections — the common cold,
pharyngitis (sore throat) and laryngitis — involve only the
upper airways (i.e. the top part of the conducting airways).
Although the lungs have direct contact with the atmosphere,
they usually remain sterile as the upper airways filter and
clear the inspired air of contaminants and thus more serious
infections are prevented. Infections of the lower respiratory

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 733

virus and parainfluenza virus are common aetiological
microorganisms. Legionella species is also an important
cause of community-acquired pneumonia. Pseudomonas
aeruginosa, other gram-negative microorganisms and
Staphylococcus aureus are the most common aetiological
agents in hospital-acquired pneumonia. Immunocompromised
individuals (e.g. people with HIV or individuals who have
undergone organ transplantation) are especially susceptible
to Pneumocystis jiroveci, mycobacterial infections and fungal
infections, such as aspergillus, of the respiratory tract. These
infections can be difficult to treat and have a high mortality
rate.

PAT H O P HYS I O LO G Y
Aspiration of oropharyngeal secretions is the most common
route of lower respiratory tract infection; thus, the
nasopharynx and oropharynx constitute the first line of
defence for most infectious agents. Another route of infection
is through the inhalation of microorganisms that have been
released into the air when an infected individual coughs,
sneezes or talks, or from aerosolised water such as that
from contaminated respiratory therapy equipment. This
route of infection is most important in viral and mycobacterial
pneumonias and in Legionella outbreaks. Pneumonia can
also occur when bacteria are spread to the lungs in the
blood from bacteraemia (bacteria within the blood) that
can result from infection elsewhere in the body or from
intravenous drug abuse.

In healthy individuals, pathogens that reach the lungs
are expelled or held in check by mechanisms of defence
(see Chapters 12 and 13). If a microorganism gets past the
upper airway defence mechanisms, such as the cough reflex
and mucociliary escalator, the next line of defence is the
alveolar macrophage (see Chapter 24 for details on
pulmonary system defence mechanisms). This phagocyte
is capable of removing most infectious agents without setting
off significant inflammatory or immune responses. However,
if the microorganism is virulent (small numbers can be
pathogenic) or present in large enough numbers, it can
overwhelm the alveolar macrophages. This results in a
full-scale activation of the body’s defence mechanisms,
including the release of multiple inflammatory mediators,

tract occur most often in individuals whose normal defence
mechanisms are impaired and often provide more serious
alterations to the pulmonary system, which can also have
profound systemic effects, such as changes in cellular
metabolism, affecting homeostasis. Of all the pulmonary
infections in adults, pneumonia is the most serious and a
leading cause of death in both males and females in Australia
and New Zealand, especially in people older than 65 years
of age.44 We now examine the pathophysiology of this serious
infection.

Pneumonia
Pneumonia is infection of the lower respiratory tract caused
by bacteria, viruses, fungi, protozoa or parasites. Risk factors
for pneumonia include advanced age, individuals who are
immunocompromised, underlying lung disease, alcoholism,
altered consciousness, smoking, malnutrition and
immobilisation. The causative microorganism influences
how the individual presents clinically, how the pneumonia
should be treated and the prognosis. Community-acquired
pneumonia tends to be caused by different microorganisms
compared to healthcare-acquired infections (healthcare-
acquired infections are discussed in Chapter 14). In addition,
the characteristics of the individual are important in
determining which microorganism is likely to infect them;
for example, immunocompromised individuals tend to be
susceptible to opportunistic infections (pathogens that cause
infections but not in healthy individuals) that normally are
uncommon in adults. In general, infections acquired within
healthcare facilities and those affecting immunocompromised
individuals have a higher mortality rate than community-
acquired pneumonia. Some of the most common causal
microorganisms are listed in Table 25.4.

The most common community-acquired pneumonias
are caused by bacteria, particularly those caused by
Streptococcus pneumoniae (also known as the pneumococcus),
which has a relatively high mortality rate in the elderly.
Mycoplasma pneumoniae is a common cause of pneumonia
in young people living in close contact, such as in dormitories.
Influenza is the most common viral community-acquired
pneumonia in adults and children; respiratory syncytial

TABLE 25.4 Common microorganisms of pneumonia

COMMUNITY-ACQUIRED PNEUMONIA HEALTHCARE-ACQUIRED PNEUMONIA IMMUNOCOMPROMISED INDIVIDUALS

Streptococcus pneumoniae Pseudomonas aeruginosa Pneumocystis jiroveci (Pneumocystis pneumonia)

Mycoplasma pneumoniae Staphylococcus aureus Mycobacterium tuberculosis

Haemophilus influenzae Klebsiella pneumoniae Atypical mycobacteria

Oral anaerobic bacteria Escherichia coli Fungi

Influenza virus Respiratory viruses

Legionella pneumophilae Protozoa

Chlamydia pneumoniae Parasites

Moraxella catarrhalis

734 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

further diagnostic studies may include bronchoscopy (in
which a scope with a camera is introduced into the lungs
to visualise the airways) or lung biopsy. Positive identification
of viruses can be difficult. Blood cultures often help to
identify the virus if systemic disease is present.

Antibiotics are used to treat bacterial pneumonia;
however, resistant strains of pneumococcus are on the rise.
Antibiotics are chosen based on the likely causative
microorganism according to the clinical presentation and
history. Viral pneumonia is usually treated with supportive
therapy alone; however, antiviral medication may be needed
in severe cases. Infections with opportunistic microorganisms
may be polymicrobial (many species of microorganism)
and require multiple drugs, including antifungals. Adequate
hydration and good pulmonary hygiene (e.g. deep breathing,
coughing, chest physiotherapy) are important aspects of
treatment for all types of pneumonia.

Tuberculosis
Tuberculosis, commonly abbreviated to TB, is an infection
caused by Mycobacterium tuberculosis, a bacterium that
usually affects the lungs but may invade other body systems.
Worldwide, tuberculosis is the leading cause of death from
a curable infectious disease and was responsible for an
estimated 1.8 million deaths in 2015.45 There are new cases
of tuberculosis each year in Australia and New Zealand
although the rates are very low compared with other
developed countries. In 2012 there were 1317 cases of TB
reported in Australia; these data represent a rate of 5.8
cases for every 100 000 people. Alarmingly the incidence
rates of TB among the Indigenous population was five times
that of the non-Indigenous Australian-born population in
2012 and 2013.45

PAT H O P HYS I O LO G Y
Tuberculosis (TB) is transmitted from person to person in
airborne droplets. Microorganisms lodge in the lung
periphery, usually in the upper lobe. Once the bacteria are
inspired into the lung, they multiply and cause lung
inflammation. Some bacteria migrate through the lymphatics
and become lodged in the lymph nodes, where they
encounter lymphocytes that initiate the immune response.
The infection can either be active or latent.

Inflammation in the lung causes activation of alveolar
macrophages and neutrophils. These cells engulf the bacteria
and begin the process by which the body’s defence
mechanisms isolate and prevent their spread. The neutrophils
and macrophages seal off the colonies of bacteria, forming
granulomatous lesions called tubercles. Infected tissues
within the tubercles die, forming cheese-like material that
is necrotic (see Fig. 25.21).46 Scar tissue then grows around
the tubercles, completing isolation of the bacteria. The
immune response is complete after about 10 days, preventing
further spread of the bacteria.

Once immunity develops, tuberculosis may remain
dormant for life.46 If the immune system is impaired or if
live bacteria escape into the bronchi, active disease occurs

cellular infiltration and immune activation. These
inflammatory mediators and immune complexes can damage
bronchial mucous membranes and alveolar–capillary
membranes, causing the alveoli and terminal bronchioles
to fill with infectious debris and exudate (fluid moving into
a site of inflammation). In addition, some microorganisms
release toxins from their cell walls that can cause further
lung damage. The accumulation of exudate in the alveoli
leads to dyspnoea, ventilation–perfusion mismatching and
hypoxaemia.

There are many viruses that can cause pneumonia,
including influenza virus, respiratory syncytial virus,
adenoviruses and parainfluenza virus. Viral pneumonia is
the primary cause of pneumonia in children and older
adults. Although viral pneumonia can be severe, it is usually
mild and self-limiting. However, it can set the stage for a
secondary bacterial infection by providing an ideal
environment for bacterial growth and by damaging ciliated
epithelial cells, which normally prevent pathogens from
reaching the lower airways. Viral pneumonia can be a
primary infection or a complication of another viral illness,
such as chickenpox or measles (spread from the blood).
The virus not only destroys the ciliated epithelial cells but
also invades the goblet cells and bronchial mucous glands.
Sloughing of destroyed bronchial epithelium occurs
throughout the respiratory tract, preventing mucociliary
clearance. Bronchial walls become oedematous and infiltrated
with leucocytes. In severe cases, the alveoli are involved,
with decreased compliance and increased work of breathing.

C L I N I C A L MA N I F E S TAT I O N S
Many cases of pneumonia are preceded by an upper
respiratory infection, which is often viral. Individuals then
develop fever, chills, productive or dry cough, malaise,
pleural pain and sometimes dyspnoea and haemoptysis
(blood in the sputum). Physical examination may reveal
signs of pulmonary consolidation, such as dullness to
percussion (creation of vibrations, typically by tapping the
chest) and inspiratory crackles. Individuals may also
demonstrate symptoms and signs of underlying systemic
disease or sepsis.

E VA LUAT I O N A N D T R E AT M E N T
Diagnosis is made on the basis of the physical examination,
white blood cell count, chest x-ray, stains and cultures of
respiratory secretions, and blood cultures. The white blood
cell count is usually elevated, although it may be low if the
individual is debilitated or immunocompromised. Chest
x-rays show infiltrates that may involve a single lobe of the
lung or may be more diffuse (see Fig. 25.20). Once the
diagnosis of pneumonia has been made, the pathogen is
identified by means of sputum characteristics (gram stain;
see Chapter 14 for details) and cultures or, if sputum is
absent, blood cultures. Because many pathogens exist in
the normal oropharyngeal flora, the specimen may be
contaminated with pathogens from oral secretions. If sputum
studies fail to identify the pathogen, the individual is
immunocompromised or the individual’s condition worsens,

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 735

recommendations of the Australian National Tuberculosis
Advisory Committee are that tuberculin skin testing be
used as the standard test for latent tuberculosis infection,
with targeted use of interferon gamma release assays
(Quantiferon Gold) when high specificity is desired.47 When
an individual becomes infected with the pathogenic bacteria,
Mycobacterium tuberculosis, the bacterial antigen is
recognised by the immune system and T cells are sensitised.
The T cells then release the cytokine, interferon gamma,
which stimulates macrophages to phagocytose bacteria (see
Chapter 13 for more details on immune responses).

Treatment consists of antibiotic therapy to control active
or latent tuberculosis infection and prevent transmission.
Today, with the increased numbers of immunosuppressed
individuals and drug-resistant bacteria, treatment is never
single drug therapy as resistance appears rapidly; the
recommended treatment includes a combination of drugs
to which the organism is susceptible, including isoniazid,
rifampin, pyrazinamide and ethambutol. Combination
therapy is usually continued for 6 months.

and may spread through the blood and lymphatics to other
organs.

C L I N I C A L MA N I F E S TAT I O N S
In people with active infection the most common clinical
features of tuberculosis include chronic cough, sputum
production, loss of appetite, weight loss, fever, night sweats,
chest pain and haemoptysis. Individuals with latent infection
are usually asymptomatic; however, they remain at risk of
reactivation of tuberculosis in their lifetime.

E VA LUAT I O N A N D T R E AT M E N T
Tuberculosis is usually diagnosed by a positive tuberculin
skin test, sputum culture and chest x-rays. However, due
to the high rate of false positives with the tuberculin skin
test (meaning that the test reveals a positive tuberculosis
result when the disease is not present), newer diagnostic
tests have been developed. One such test, the interferon
gamma release assay, measures interferon gamma that has
been released from T cells of the immune system. The

Bronchopneumonia

Lobar pneumonia

A
B

FIGURE 25.20

Bacterial pneumonia seen in gross lung, chest x-ray and illustration.
A Lobar pneumonia occurs when bacterial infection occurs in a portion of the lobe or the entire lobe. B Bronchopneumonia with patchy
consolidation throughout the lung.

736 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

of the airways is usually caused by viruses, whereas the
chronic airway inflammation is mainly caused by smoking.
Acute bronchitis is likely to lead to a full recovery once
the inflammation is resolved, whereas chronic bronchitis is
irreversible. Many clinical manifestations of acute bronchitis
are similar to those of pneumonia (fever, cough, chills and
malaise — a general feeling of being unwell), but chest
x-rays show no infiltrates. Individuals with viral bronchitis
present with a non-productive cough that often occurs in
paroxysms (sudden fits of coughing) and is aggravated by
cold, dry or dusty air. In some cases, purulent sputum is
produced. Chest pain often develops from the effort of
coughing. Treatment consists of rest, aspirin, humidity and
a cough suppressant, such as codeine.51

Bacterial bronchitis is rare in previously healthy adults
except after viral infection but is common in patients with
COPD. Although individuals with bronchitis do not have
signs of pulmonary consolidation on physical examination
(e.g. crackles), many will require chest x-ray evaluation to
exclude the diagnosis of pneumonia. Bacterial bronchitis
is treated with rest, antipyretics (fever-reducing drugs) and
antibiotics.

Influenza
Influenza is a common respiratory viral infection that
affects millions of people worldwide.1 The influenza virus
can infect all age groups. There are a number of groups
that are at a higher risk of influenza including the elderly;
adults and children (aged 6 months and over) with chronic
disorders of the pulmonary or circulatory systems, and
nursing home and long-term-care residents. The virus can
rapidly spread worldwide and has a seasonal variation that
affects Australia and New Zealand predominately from June
to September.44,52

PAT H O P HYS I O LO G Y
There are three main strains of influenza virus: type A, type
B and type C. All three can cause influenza in humans, but
type A is the most prevalent and is responsible for the
yearly influenza known as ‘seasonal flu’. Type A has many
different subtypes, which are classified using the letters ‘H’
and ‘N’, denoting two different surface proteins. For example,
the most common virus causing infection in humans is
type A (H1N1), which itself has many different subtypes.
However, the virus can change — called antigenic drift,
which means that mutations occur in the virus antigen
such that the body’s antibodies cannot recognise the virus
and hence it represents a new primary immune response.
This is the primary reason why ‘new’ types of flu circulate
each year. Antigenic drift has led to major pandemics that
have resulted in massive mortality worldwide. Alarmingly,
type A affects not only humans, but also horses, pigs, birds
and aquatic birds. Avian and swine type A influenza have
infected humans, and human-to-human transmission has
occurred, leading to pandemics.

The influenza virus enters the upper airways from
airborne secretions of an infected individual. If the virus is

In the past, individuals with active tuberculosis were
isolated from the community. Today, individuals remain
at home or, rarely, in hospital, until sputum cultures show
that the active disease has been eliminated. Directly observed
therapy short courses (DOTS) has been integral in the
control of tuberculosis worldwide.48 DOTS involves five
elements: political commitment; microscopy services; drug
supplies; surveillance and monitoring systems and use of
highly efficacious regimens; and direct observation of
treatment.49 Building on this the World Health Organization
has developed the END TB Strategy which aims to end the
global tuberculosis epidemic.50

Acute bronchitis
Acute bronchitis is an acute infection or inflammation of
the airways or bronchi and is usually self-limiting. In the
vast majority of cases, it is caused by viruses.51 It differs from
chronic bronchitis of COPD, in that acute inflammation

FIGURE 25.21

Tuberculosis in the lung.
The grey-white areas represent the lesions formed from the bacteria.

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 737

not immobilised by the inflammatory and immune systems,
it invades the respiratory tract lining and proliferates. The
triggered inflammatory mediators cause mucosal hyperaemia
(redness to the mucosal lining), upper airway oedema and
excess mucous secretion. The incubation period (until the
appearance of symptoms) is up to 72 hours.

C L I N I C A L MA N I F E S TAT I O N S
The classic signs and symptoms of cough and fever are
usually indicative of influenza infection. They are often
accompanied by generalised myalgia (muscle pain), headache
and sore throat. The onset of the illness is abrupt and usually
lasts between 3 and 5 days. Influenza infections can invade
the lower respiratory tract and cause pneumonia, especially
in children, the elderly and immunocompromised individuals
(see Fig. 25.22).

E VA LUAT I O N A N D T R E AT M E N T
Diagnosis of influenza is often difficult because of the rapid
onset and relatively short duration. In addition, it is often
hard to obtain isolation of the virus in specimens. The most
effective treatment is prevention. Handwashing combined
with pulmonary hygiene lowers the risk of acquiring the
virus. In Australia and New Zealand, influenza vaccines
are available for those at higher risk of attaining the virus,
such as healthcare workers, those with chronic illnesses,
infants and the elderly.

FIGURE 25.22

Chest x-ray changes in a patient with influenza pneumonia.
The primary chest x-ray changes include small multifocal, patchy
consolidations throughout both lungs, predominantly in the bases.

P
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Paediatrics and pulmonary infections
Respiratory infections are common in children and are
a frequent cause of hospitalisations. Clinical presentation,
the age of the child and the season of the year can often
provide clues to the type of microorganism, even when
the agent cannot be proven.

Bronchiolitis
Bronchiolitis is a rather common, viral-induced lower
respiratory tract infection that occurs almost exclusively
in infants and young toddlers. It has a seasonal, yearly
incidence (May–October) and is the leading cause of
hospitalisations for infants during the winter season. The
most common associated pathogen is respiratory syncytial
virus, which accounts for 50–80% of hospitalisations,53
but it may also be associated with human rhinovirus,
adenoviruses, influenza, parainfluenza and mycoplasma.
Healthy infants usually make a full recovery from
respiratory syncytial virus bronchiolitis, but infants who
were born premature with a birth weight of less than
2500 grams have a much higher risk for a more severe
or even fatal course.

PATHOPHYSIOLOGY
Viral infection causes necrosis of the bronchial epithelium
and destruction of ciliated epithelial cells. There is
infiltration with lymphocytes around the bronchioles
and a cell-mediated hypersensitivity to viral antigens
with release of lymphokines causing inflammation, as
well as activation of eosinophils, neutrophils and
monocytes. The submucosa becomes oedematous and
cellular debris and fibrin form plugs within the
bronchioles.
Oedema of the bronchiolar wall, accumulation of
mucus and cellular debris and, perhaps, bronchospasm
narrow many peripheral airways. Other airways become
partially or completely occluded. Atelectasis (collapse
of lung tissue) occurs in some areas of the lungs and
hyperinflation in others. There is air trapping and
functional residual capacity is greatly increased.
Compliance is decreased because the lungs are already
highly inflated and because airway resistance within the
lungs is uneven and increased. The decrease in compliance
and the increase in airway resistance result in a substantial

Continued

738 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

Australia, lung cancer incidence and mortality in females
is projected to rise, while the rates for males are in decline.

The most common cause of lung cancer is cigarette
smoking, being linked to approximately 70% of cases in
females and 90% in men. It has been shown that the number
of cigarettes that people smoke and the number of years
they smoke are directly related to the risk of developing
lung cancer. There is an increased risk of developing lung
cancer with advancing age, with a three times greater risk
in people aged 65 years and older compared with their
younger counterparts. This is evidenced by the fact that
only 1% of lung cancers occur in people less than 40 years
of age.56 In addition, second-hand (passive or environmental)
smoke exposure is also a risk for lung cancer, so an individual
exposed to the smoke from someone else’s cigarettes also
has this increased risk. Smokers with obstructive airway
disease (low FEV1) are at even greater risk. Genetic
predisposition to developing lung cancer also plays a role
in the pathophysiology. Other risk factors include
occupational exposure to certain workplace toxins, radiation,
air pollution and tuberculosis.

Types of lung cancer
Primary lung cancers arise from the bronchi within the
lungs and are therefore called bronchogenic carcinomas.
Although there are many types of lung cancer, lung cancer
is divided into two major categories: non-small cell
carcinoma (75–85% of all lung cancers) and small cell
carcinoma (15–25% of all lung cancers). The category
non-small cell carcinoma can be subdivided into three

Lung cancer
Lung cancer arises from the epithelium of the respiratory
tract. Therefore, the term lung cancer excludes other
pulmonary tumours such as sarcomas, lymphomas,
blastomas, haematomas and mesotheliomas.

In 2010 more than 8000 people died from lung cancer
in Australia.56 Of all the cancers, lung cancer is the leading
cause of death in Australia.56 Since 2006 the number of
lung cancer-related deaths has exceeded breast cancer, and
while there has been a decline in mortality from most cancers
between 1991 and 2010 the mortality rate from lung cancer
in the female population has continued to rise.56 The
incidence and mortality rates of lung cancer in the
Indigenous population are approximately double those of
the non-Indigenous population. Concomitantly, smoking
rates in the Indigenous population are also greater.56

In New Zealand, lung cancer is the most common cause
of cancer death for both males and females.57 Similarly in

increase in the work of breathing. Serious alterations
in gas exchange occur because of airway obstruction
and patchy atelectasis. Hypoxaemia develops because of
ventilation–perfusion mismatch and hypercapnia may
occur in severe cases. It has been suggested that children
with acquired bronchiolitis may later develop asthma, but
the relationship between these two respiratory disorders
is unclear.

CLINICAL MANIFESTATIONS
Symptoms usually begin with significant rhinorrhoea
(runny nose) followed by a tight cough over the next
few days, along with systemic signs of poor feeding,
lethargy and fever. Infants typically have tachypnoea
(increased ventilatory rate), variable degrees of respiratory
distress and abnormal auscultatory findings of the chest.
Wheezing is most common.

EVALUATION AND TREATMENT
Diagnosis of bronchiolitis is made by a review of the
signs and symptoms (e.g. rhinitis, cough, wheezing, chest
retractions, tachypnoea) and chest x-ray findings.

Treatment is determined by the severity of the disease
and the age of the child. Most cases are mild and usually
require no specific treatment. Preventive treatment using
pulmonary and hand hygiene combined with decreased
exposure to people in the susceptible months decreases
the risk of infection. Respiratory syncytial virus antibody
is recommended for high-risk infants under 2 years old.54

Pertussis
Pertussis is caused by the bacterium Bordetella pertussis.
The symptoms are thick secretions, a chronic cough and
spasm following coughing fits, which give a characteristic
‘whoop’ sound — hence the commonly used name
‘whooping cough’. The infection has an incubation period
of 7–10 days and is highly contagious, but vaccination
can prevent the infection. However, despite the availability
of a vaccine, Australia and New Zealand experience
periodic outbreaks of pertussis, with 11 863 cases reported
in Australia in 2014.55 Pertussis is particularly lethal in
newborns and infants who are too young to have received
two or more doses of the vaccine (see Chapter 14 for
immunisation schedules).

F O C U S O N L E A R N I N G

1 Differentiate between different pneumonias.

2 Discuss the effects of tuberculosis on pulmonary
structures.

3 Discuss why influenza virus is virulent and can lead to
pandemics.

4 Describe the typical presentation of respiratory syncytial
virus bronchiolitis.

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 739

non-productive cough or haemoptysis (which is the coughing
up of blood in the sputum; see ‘Clinical manifestations of
pulmonary alterations’ below). Pneumonia and atelectasis
are often associated with squamous cell carcinoma. Chest
pain is a late symptom associated with large tumours. These
tumours can remain fairly well localised and tend not to
metastasise until late in the course of the disease. The
preferred treatment is surgical resection, although once
metastasis (spread away from the original site) has taken
place, total surgical resection is more difficult and survival
rates decrease dramatically.58 Radiation therapy and
chemotherapy improve outcomes in many individuals.

Adenocarcinoma (meaning that the tumour arises from
the glands) constitutes 35–40% of all bronchogenic
carcinomas (see Fig. 25.24). The increase in incidence of
adenocarcinoma has been ascribed to the increasing
occurrence of lung cancer in females, environmental and
occupational carcinogens, and changes in the histological
criteria for diagnosis. These tumours, which are usually
smaller than 4 cm, more commonly arise in the peripheral
regions of the lung tissue. They may be asymptomatic and
discovered by routine chest x-ray in the early stages or the
individual may present with pleuritic chest pain and
shortness of breath from pleural involvement by the tumour.
Surgical resection is possible in a high proportion of cases,
but because metastasis occurs early, the 5-year survival rate
is low.

Large cell carcinomas constitute 10–15% of bronchogenic
carcinomas (see Fig. 25.25). This cell type has lost all
evidence of differentiation and therefore is sometimes
referred to as undifferentiated large cell anaplastic cancer
(literally meaning that the cells revert back to an immature
form). Because large cell carcinomas show none of the
histological findings of squamous cell carcinoma or

common types of lung cancer: squamous cell carcinoma,
adenocarcinoma and large cell carcinoma. Characteristics
of these tumours, including the clinical manifestations, are
listed in Table 25.5. Many cancers that arise in other organs
of the body metastasise to the lungs; however, these are
not considered as lung cancers and are categorised by their
primary site of origin.

Non-small cell carcinoma
Squamous cell carcinoma accounts for about 30% of
bronchogenic carcinomas. These tumours are typically
located near the hilum and project into the bronchi (see
Fig. 25.23). Because of the location in the central bronchi,
obstructive manifestations are nonspecific and include

TABLE 25.5 Characteristics of lung cancers

TUMOUR TYPE GROWTH RATE METASTASIS DIAGNOSIS CLINICAL MANIFESTATIONS

Non-small cell carcinoma
Squamous cell
carcinoma

Slow Late; mostly to hilar
lymph nodes

Biopsy, sputum analysis,
bronchoscopy, electron
microscopy

Cough, haemoptysis, sputum
production, airway obstruction,
hypercalcaemia

Adenocarcinoma Moderate Early; to lymph nodes,
pleura, bone, adrenal
glands and brain

Radiography, fibreoptic
bronchoscopy, electron
microscopy

Pleural effusion

Large cell
carcinoma

Rapid Early and widespread Sputum analysis, bronchoscopy,
electron microscopy (by
exclusion of other cell types)

Chest wall pain, pleural effusion,
cough, sputum production,
haemoptysis, airway obstruction
resulting in pneumonia

Small cell carcinoma
Very rapid Very early; to

mediastinum, lymph
nodes, brain, bone
marrow

Radiography, sputum analysis,
bronchoscopy, electron
microscopy

Cough, chest pain, dyspnoea,
haemoptysis, localised wheezing,
airway obstruction, signs and
symptoms of excessive hormone
secretion

FIGURE 25.23

Squamous cell carcinoma.
A Normal carina and bronchi of left upper lobe. B Carina of left
lower lobe with swollen mucosa (thin dark line showing extent of
swelling), white lesion (squamous cell cancer, bottom arrow) and
haemorrhage on upper surface (top arrow).

740 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

B
A

FIGURE 25.25

Large cell carcinoma.
A Gross lung with a large white-grey mass on lower right margin.
B Chest x-ray of a large cell carcinoma in the right lower lobe (red
arrow).

FIGURE 25.24

Adenocarcinoma.
This gross lung lobe has a large white mass (carcinoma). The
cancers are predominately on the peripheral aspects of the lung,
not in the large airways.

adenocarcinoma, they are diagnosed by a process of
exclusion. The cells are large and contain darkly stained
nuclei. These tumours commonly arise centrally and can
grow to distort the trachea and cause widening of the carina,
which can result in breathing difficulties. Once metastasis
has occurred, surgical therapy is limited to palliative
procedures — meaning that care is for comfort only, as the
individual cannot be cured.

Small cell carcinoma
Small cell carcinomas constitute 15–20% of bronchogenic
carcinomas. Most of these tumours are central in origin
(see Fig. 25.26). This cell type has the strongest correlation
with cigarette smoking. Because these tumours show a rapid
rate of growth and tend to metastasise early and widely,
small cell carcinomas have the worst prognosis. Survival
time for untreated small cell carcinoma is usually only 1–3
months. Approximately only 14% of treated individuals are
alive 2 years after diagnosis.

Small cell carcinoma is most often associated with ectopic
hormone production, meaning that hormones are produced
in tissues, in this case cancerous lung tissue, away from the
usual glands. Neuroendocrine cells containing neurosecretory
granules exist throughout the tracheobronchial tree and
may be associated with small cell carcinoma. Ectopic
hormone production is important to the clinician because
resulting signs and symptoms may be the first manifestation

of the underlying cancer. Small cell carcinomas most
commonly produce antidiuretic hormone from associated
neuroendocrine cells and develop the syndrome of
inappropriate antidiuretic hormone secretion. Individuals
with lung cancer secrete large quantities of steroids, leading
to the development of an atypical Cushing’s syndrome (see
Chapter 11).

Signs and symptoms related to this condition include
muscular weakness, facial oedema, hypokalaemia, alkalosis,
hyperglycaemia, hypertension and increased pigmentation.
Treatment of small cell carcinoma is usually palliative. More
than 85% of tumours will have metastasised by the time
of diagnosis. Chemotherapy and radiation can significantly
prolong life and relieve symptoms, but relapse is inevitable
in most individuals.59

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 741

cell type, and the evaluation of lymph nodes and other
organ systems is used to determine the stage of the cancer.
The histological cell type and the stage of the disease are
the major factors that influence the choice of therapy. The
current accepted system for the staging of non-small cell
carcinoma is the TNM classification. This system is a code
in which T denotes the extent of the primary tumour, N
indicates the lymph node involvement and M describes the
extent of metastasis. Small cell carcinoma is so rapidly
progressive that its staging system consists of only two stages:
limited and extensive disease.

The only proven way of reducing the risk for lung cancer
is the cessation of smoking. To date, trials evaluating the
use of various early screening modalities such as chest x-ray
and CT scanning have not resulted in a decrease in lung
cancer mortality.61 The management of lung cancer has
been outlined here under each cell type, but it is generally
chosen on the basis of tumour stage and patient functional
status. Current modalities include combinations of surgical
resection, chemotherapy and radiation; however, new genetic
and immunological therapies are being explored (see
‘Research in Focus: Genetic and immunological therapies
for lung cancer’).

PAT H O P HYS I O LO G Y
Tobacco smoke contains more than 30 carcinogens and
is responsible for causing 80–90% of lung cancers. These
carcinogens result in multiple genetic abnormalities in
bronchial cells including deletions of chromosomes, activation
of oncogenes and inactivation of tumour suppressor genes.
The most common genetic abnormality associated with lung
cancer is loss of the tumour suppressor gene p53; mutations
in this gene have been found in 50–60% of non-small cell
carcinomas and 90% of small cell carcinomas.60 Once lung
cancer is initiated by these carcinogen-induced mutations,
further tumour development is promoted by growth factors.
Further cellular toxicity is enhanced through smoke-induced
toxic free radical production.

The bronchial mucosa suffers multiple carcinogenic ‘hits’
due to repetitive exposure to cigarette smoke and eventually
epithelial cell changes begin to be visible on biopsy. These
changes progress from metaplasia (changing from one
cell type to another cell type) to carcinoma in situ and
finally to invasive carcinoma. Further tumour progression
includes invasion of surrounding tissues and finally
metastasis to distant sites including the brain, bone marrow
and liver.

C L I N I C A L MA N I F E S TAT I O N S
There are many different signs and symptoms in individuals
with lung cancer. It is somewhat dependent on the location
of the cancer in the pulmonary system as to what clinical
manifestations will arise. Table 25.5 summarises the
characteristic clinical manifestations according to tumour
type. By the time there are manifestations severe enough
for the individual to notice them, the disease is usually
advanced.

E VA LUAT I O N A N D T R E AT M E N T
Diagnostic tests for the evaluation of lung cancer include
chest x-ray, sputum cytology, chest-computed tomography,
fibreoptic bronchoscopy and biopsy. Biopsy determines the

FIGURE 25.26

Small cell carcinoma.
The cancer can be seen as the white growths.

R E S E A R C H I N F C U S
Genetic and immunological therapies for
lung cancer
Although new chemotherapeutic agents have slightly
improved outcomes in the management of lung cancer,
overall survival rates remain poor and the toxicities of these
regimens limit their use. New understandings of the genetic
and immunological features of lung cancer cells have led to
new treatments. Gene therapy is emerging as a way of
restoring normal tumour suppressor gene function and
increasing tumour responsiveness to chemotherapy and
radiation therapy. Immunological therapies include antibodies
to growth factor receptors and anti-angiogenesis drugs (those
that prevent the growth of new blood vessels from the
tumour). The effectiveness of these strategies is still being
evaluated, but new knowledge is leading to new opportunities
for treatment.

F O C U S O N L E A R N I N G

1 Describe the incidence and mortality of lung cancer and
the differences between the sexes.

2 Discuss the pathological differences between non-small
cell carcinoma and small cell carcinoma.

742 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

PAT H O P HYS I O LO G Y
Anatomical and structural factors in the upper airway play
a crucial role in the development of obstructive sleep apnoea.
The tonsils, adenoids, tongue and soft tissue that surround
the pharynx become enlarged, reducing the lumen (airway
size). This is more pronounced in obese individuals who
have a large neck circumference. Collectively, these factors
predispose the individual to upper airway collapse during
sleep.69 In children, the most pathophysiological reason for
obstructive sleep apnoea is due to adenotonsillar hypertrophy;
however, rates of childhood obesity are also likely to
contribute to the rates of childhood sleep apnoea.

When obstructive sleep apnoea is present, the pharyngeal
tissue completely obstructs the airway, preventing ventilation.
This causes a cycle of obstructive breathing during sleep
when the airway repeatedly collapses, and this periodic
breathing eventually produces arousal, which interrupts
the sleep cycle, reducing total sleep time and producing
sleep deprivation.69 The often sustained and repeated apnoeic
periods result in hypoxaemia (inadequate oxygen levels in
the blood), which, it has been proposed, influences neural
control of the upper airway. Hypoxaemia is more pronounced
during periods of rapid eye movement (REM) sleep. The
reason for this is unknown, but it may explain the tiredness
and insomnia reported by individuals with obstructive sleep
apnoea.

Sleep apnoea produces low oxygen saturation (see Fig.
25.27) and eventually leads to polycythaemia (a blood

Obstructive sleep apnoea
Obstructive sleep apnoea generally results from upper
airway obstruction recurring during sleep, with excessive
snoring and multiple apnoeic episodes (periods were there
is no breathing) that last at least 10 seconds but can last
up to 60 seconds or more. Approximately 9–25% of the
middle-aged population in Australia have obstructive sleep
apnoea,62 and the prevalence in older people is likely to be
higher as sleep complaints and disorders are more common
in the elderley.63 In New Zealand, the prevalence of
obstructive sleep apnoea has been estimated at 4.1% for
males and 0.7% for females.64 Within Indigenous populations,
the prevalence is higher for both males and females.
Childhood obstructive sleep apnoea is also quite common,
with an estimated prevalence of 1–10%.65 In children, unlike
in adults, obstructive sleep apnoea occurs equally among
girls and boys.

There is an increased risk of death from cardiovascular
disease associated with obstructive sleep apnoea.66 The exact
reason for this is unknown; however, the repeated episodes
of hypoxia related to apnoea during sleep are likely to impact
on the cardiovascular system. It has also been shown that
obstructive sleep apnoea is an independent risk factor for
increased mortality from any cause.67 Other deleterious
consequences of obstructive sleep apnoea include
unrefreshing sleep, excessive daytime sleepiness and
neurocognitive impairment.68

100

Sp
O

2
(
%

)
100
90
80
70
60
50
Sp
O
2
(
%
)

11:00 pm 1 am 3 am 4 am 5 am 6 am2 am
Time (clock)

12 Midnight

A
B

FIGURE 25.27

Oxygen saturation levels during sleep apnoea.
Oxygen saturation (SpO2) levels during sleep in A a healthy individual, and B an individual with severe obstructive sleep apnoea. In the
healthy individual, oxygen saturation remains close to 100%. With the individual with sleep apnoea, the large reductions in oxygen
saturation during sleep are due to the repeated apnoea episodes.

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 743

and alcohol consumption.69 The most accurate diagnosis
of obstructive sleep apnoea is an overnight polysomnogram,
also known as a sleep study.70 This test records brain activity
(electroencephalogram), eye movement, muscle activity
(electromyogram), heart rate, air flow and oxygen
haemoglobin (SpO2) levels during sleep and collectively
allows classification of the amount and duration of apnoeic
periods, thereby permitting diagnosis of obstructive sleep
apnoea.

Treatments include nasal continuous positive airway
pressure (CPAP) and dental devices, upper airway and
jaw surgery in selected individuals, and management
of obesity.70 In children, if obstructive sleep apnoea is
documented or strongly suspected clinically, tonsillectomy
and adenoidectomy are the treatments of choice. For severely
affected children who do not respond to surgery or who
have different problems, such as obesity, that cannot be
remedied rapidly, CPAP, similar to adult management, may
be required.

disorder causing excessive red cell production), pulmonary
hypertension, right-sided heart failure, liver congestion,
cyanosis and peripheral oedema. Systemic hypertension
may result from repeated episodes of apnoea and hypoxaemia.

C L I N I C A L MA N I F E S TAT I O N S
Due to obstruction of the upper airway, snoring is the most
common manifestation. There may be periods of increased
ventilatory effort without an audible airflow. During the
apnoeic periods, breathing can cease for 10 seconds up to
1 minute and these episodes can occur repeatedly throughout
sleep.70 Therefore, sleep is often restless, and there is daytime
tiredness and sleepiness. This chronic tiredness impacts on
daytime cognitive and neurobehavioural performance. For
instance, obstructive sleep apnoea has been associated with
an increased mortality from traffic accidents.69 Cardiac
arrhythmias during sleep apnoea are common, such as sinus
pauses (temporary cessation of sinus node activity) and
premature ventricular contractions.71 In children, bedwetting
and chronic mouth breathing are associated with obstructive
sleep apnoea.

E VA LUAT I O N A N D T R E AT M E N T
There usually is a history of snoring and laboured breathing
during sleep, which may be continuous or intermittent in
individuals with obstructive sleep apnoea. Associated risk
factors include advancing age, obesity, gender (males are
more affected than females), genetic predisposition, smoking

F O C U S O N L E A R N I N G

1 Describe the signs and symptoms suggestive of
obstructive sleep apnoea in children and adults.

2 Discuss the effect of sleep apnoea on daytime activities.

P
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Paediatrics and pulmonary disorders
There are some important childhood pulmonary disorders
that need to be explored. In this section we examine
some of the major childhood disorders, starting with
croup.
Croup
Classic croup is an acute inflammation of the upper
airways and almost always occurs in children between
3 months and 5 years of age.72 In 85% of cases, croup is
caused by a virus, most commonly parainfluenza and in
other instances by influenza A or respiratory syncytial
virus, however bacteria and atypical agents have also
been identified.72 The incidence of croup is higher in
males and is most common during the winter months.
PATHOPHYSIOLOGY
Airway obstruction occurs in the subglottic region of
the trachea, just below the vocal cords. Contributory
factors include mucosal oedema and secretions related
to the viral infection. Anatomically, the subglottic region
is slightly narrower than the rest of the trachea and in
children the subglottic mucous membrane is more loosely
attached and more vascular than in adults. These factors
make the airway susceptible to compromise in children.

If there is significant narrowing of the airway in this
area, work of breathing will increase and the excessive
negative pressure generated may even cause the airway
structures higher up to collapse with inspiration (see
Fig. 25.28). The turbulent flow across this obstruction
will cause stridor (an abnormal, harsh, high-pitched
sound caused by turbulent flow in a partially obstructed
upper airway) on inspiration and sometimes also on
expiration (see Fig. 25.29). Croup tends to affect younger
children more prominently because they have smaller
airways that are therefore compromised more easily (see
Fig. 25.30).
CLINICAL MANIFESTATIONS
Typically, the child experiences rhinorrhoea, sore throat
and low-grade fever for a few days, then develops a seal-
like barking cough. Most cases resolve spontaneously
within 24–48 hours and do not warrant hospitalisation.
However, the presence of inspiratory stridor or respiratory
distress suggests a more severe situation.
EVALUATION AND TREATMENT
The degree of symptoms determines the level of treatment.
Treatment may include injected, oral or nebulised

Continued
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744 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

glucocorticoids to reduce the inflammation. The presence
of stridor at rest, moderate or severe retractions of the
chest or agitation suggests more severe disease and
requires hospitalisation for observation and treatment.
Severe obstruction requires emergency care to protect
the airway.
Respiratory distress syndrome of the newborn
The name respiratory distress syndrome of the newborn
refers to a lung disorder that remains a significant cause
of neonatal morbidity and mortality.73 It occurs almost
exclusively in premature infants. Respiratory distress
syndrome occurs in 60% of infants born at less than 28
weeks gestation, in 30% of those born at 28–34 weeks
and in fewer than 5% of those born after 34 weeks. The
incidence and death rates have declined significantly
since the introduction of antenatal steroid therapy and
postnatal surfactant therapy.74 Risk factors include
premature birth, caesarean delivery without labour, gender
(male), diabetic mother and perinatal asphyxia.

PATHOPHYSIOLOGY
Respiratory distress syndrome is caused by surfactant
deficiency and also a deficiency in alveolar surface area
for gas exchange. Surfactant is the material that lines the

Epiglottis

False cords
True cords
Subglottic

tissue
Trachea

A B

FIGURE 25.30

The larynx and subglottic trachea.
A Normal. B Narrowing and obstruction from oedema
caused by croup.

Snoring
zone

Inspiratory

stridor
zone

Voice
quality
zone

Cough
quality
zone Expiratory

stridor
zone

FIGURE 25.29

Respiratory sounds and their anatomical location.
Alterations in respiratory sounds inform about the airways
in those respective anatomical locations.

C
O
N
C
E
P
T
M

A
P Microorganism enters upper airway

In�ammatory
response

in upper airway
In�ammation and oedema

Upper airway obstruction

Resistance to air �ow

Increased intrathoracic
negative

pressure

Collapse of upper airway

if swelling enough causes

initiates
causes
increases
results in
causes

FIGURE 25.28

The formation of upper airway obstruction with croup.
Entry of the microorganisms causes upper airway
inflammation, leading to airway obstruction and collapse.

alveoli and is required for maintaining their inflation.
Without surfactant, which lowers surface tension, alveoli
would tend to collapse at the end of each exhalation.
Surfactant is not normally secreted by the alveolar cells
until approximately 30 weeks gestation. In addition to
the functional surfactant deficiency of the premature

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 745

Continued

lung, structural immaturity is a problem. Premature
infants are born with many underdeveloped and small
alveoli that are difficult to inflate. In the most extreme
premature infants, the ‘alveoli’ have thick walls and
inadequate capillary blood supply such that gas exchange
is significantly impaired. In addition, the chest wall is
weak and highly compliant and the rib cage tends to
collapse inwards with ventilatory effort. The net effect
of all these adverse factors is atelectasis (collapsed alveoli),
which is difficult for the neonate to overcome because

it requires a significant negative inspiratory pressure to
open the alveoli with each breath. The infant uses more
oxygen to sustain the work of breathing and becomes
hypoxaemic and hypercapnic (low blood oxygen and
high carbon dioxide, respectively). Hypoxia and atelectasis
cause pulmonary vasoconstriction and increase
intrapulmonary resistance. This results in hypoperfusion
of the lung and a decrease in effective pulmonary blood
flow. The pathogenesis of respiratory distress syndrome
is summarised in Fig. 25.31.

C
O
N
C
E
P

T M
A

Premature birth

presents with

results
results
leads to

leads to
leads to

leads to

leads
to develops

causes

manifest as

manifest as
results in
results in
results in

causescontributes
to

causes
causes

causes
worsens

Immature alveoli

Atelectasis

Respiratory failure

Increased pulmonary
vascular resistance

Inactivation of
surfactant

Protein leak
into airspaces

Hypoxaemia

Pulmonary
hypoperfusion

Hypoxic
vasoconstriction

Ventilation-perfusion
mismatch

Respiratory
acidosis

Hypercapnia

Inadequate alveolar
ventilation

Decreased expansion
of alveoli

Decreased surfactant
production

Decreased number
of alveoli

Metabolic acidosis

Impaired cellular
metabolism

Poor lung
compliance

FIGURE 25.31

The pathogenesis of respiratory distress syndrome of the newborn.
Premature birth leads to insufficient production of surfactant, poor lung compliance, insufficient number of alveoli and immature
alveoli. Together, these lead to a complex series of events including lung collapse (atelectasis), hypoxaemia and respiratory failure.

746 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

CLINICAL MANIFESTATIONS
Signs of respiratory distress syndrome appear within
minutes of birth. Some neonates require immediate
resuscitation because of asphyxia or severe respiratory
distress. Characteristic signs are tachypnoea (respiratory
rate over 60 breaths per minute), expiratory grunting,
intercostal and subcostal retractions, nasal flaring and
pale colour. The natural course is characterised by
progressive hypoxaemia and dyspnoea. Apnoea and
irregular respirations occur as the infant becomes fatigued
from the difficulty of breathing. The typical chest x-ray
shows diffuse, fine granular densities within the first 6
hours of life. In most cases the clinical manifestations
reach a peak within 3 days, after which there is gradual
improvement.
EVALUATION AND TREATMENT
Diagnosis is made on the basis of prematurity or other
risk factors and chest x-rays. The ultimate treatment for
respiratory distress syndrome would be prevention of
premature birth; however, this is not always possible and
often not foreseeable. Antenatal treatments with
glucocorticoids are given to women at 24–34 weeks
gestation for those at risk of premature delivery, and in
preterm labour, unless delivery is imminent.
Glucocorticoids induce a significant and rapid acceleration
of lung maturation and there is extensive evidence that
maternal steroid therapy significantly reduces the
incidence of respiratory distress syndrome and death.75
Surfactant therapy should be considered complementary
to antenatal corticosteroids.
Supportive care includes oxygen and often continuous
positive airway pressure or mechanical ventilation.
Most infants survive respiratory distress syndrome with
treatment. In many cases, recovery may be complete
within 10–14 days. However, the incidence of subsequent
chronic lung disease is significant among very low birth
weight infants.
Sudden infant death syndrome
Sudden infant death syndrome (SIDS) remains a disease
of unknown cause.76 It is defined as ‘sudden death of an
infant under 1 year of age which remains unexplained
after a thorough case investigation, including performance
of a complete autopsy, examination of the death scene
and review of the clinical history’.77

The incidence of SIDS is low during the first month
of life but sharply increases in the second month and
peaks at 3–4 months of age, then gradually declines.76 It
is more common in males (60%) than females (40%). It
almost always seems to occur during night-time sleep,
when infants are least likely to be observed. A seasonal
variation has been noted, with higher frequencies during
the winter months. This has been related to a higher
rate of respiratory tract infections during these months
and, in fact, such infections are often reported to have
preceded the death.
Clinical risk groups include babies who were preterm or
low birth weight, who were one of simultaneous multiple
births and who had siblings die of SIDS. Nevertheless,
about three-quarters of all SIDS cases have no known
predisposing clinical risk factor.
Additional risk factors fall into the categories of
socioeconomic or maternal factors and factors in the
baby’s sleeping situation. Maternal factors that predict
increased risk are maternal smoking, young maternal age
(under 20 years), less prenatal care, poverty and illicit
drug use. Risk factors that relate to the baby’s sleeping
situation are prone positioning, sleeping on a soft surface
and overheating.78 Prone sleeping has been concluded
to be a major and modifiable risk factor. Infants should
sleep on their backs, even in preference to side sleeping.
Other avoidable risk factors include sleeping on top of
any soft surface and loose bedding. Overwrapping the
infant or over-heating the room also appears to increase
risk, particularly if the infant is sleeping prone.
The aetiology of SIDS remains unknown but probably
involves a combination of predisposing factors and
external stressors.76,77

Currently, the best strategies for reducing SIDS seem
to be avoidance of all the controllable risk factors. In
Australia, infant mortality from SIDS has fallen to now
being extremely rare, with only three babies dying of
SIDS in 2012.79 The dramatic reduction from several
hundred deaths in previous years was attributed to a
successful national health education campaign that raised
awareness of the risk factors and promoted safe infant
sleeping practices, such as positioning the baby on their
back during sleeping.

F O C U S O N L E A R N I N G

1 Describe the pathophysiology of croup.

2 Discuss how the alveoli and capillaries are affected by
respiratory distress syndrome of the newborn.

3 List the risk factors for sudden infant death syndrome.

Alterations of pulmonary
blood flow and pressure
Blood flow through the lungs can be disrupted by disorders
that occlude the vessels, increase pulmonary vascular
resistance or destroy the vascular bed. The effects of altered
pulmonary blood flow and pressure range from insignificant

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 747

• embolus with infarction: an embolus that is large enough
to cause infarction (death) of a portion of lung tissue

• embolus without infarction: an embolus that is not severe
enough to cause permanent lung injury

• multiple pulmonary emboli: may be chronic or recurrent.
The pathogenesis of pulmonary embolism caused by a

thrombus is summarised in Fig. 25.33.
If the embolus does not cause infarction in the lung

tissue that is not receiving blood, the clot will be dissolved
by the fibrinolytic system (see Chapter 16) and pulmonary
function will return to normal. If pulmonary infarction
occurs, shrinking and scarring develops in the affected area
of the lung.

C L I N I C A L MA N I F E S TAT I O N S
In most cases, the clinical manifestations of pulmonary
embolism are nonspecific, so evaluation of risk factors and
predisposing factors is an important aspect of diagnosis.
Although most emboli originate from clots in the lower
extremities, specifically the iliac and femoral veins,80 deep
vein thrombosis is often asymptomatic and clinical
examination has low sensitivity for the presence of clot,
especially in the thigh.

An individual with pulmonary embolism usually presents
with the sudden onset of chest pain, dyspnoea, tachypnoea,
tachycardia and unexplained anxiety. Occasionally syncope
(fainting) or haemoptysis occurs. With large emboli, a pleural
friction rub, pleural effusion, fever and leucocytosis may
be noted. Recurrent small emboli may not be detected until
progressive incapacitation, precordial pain (stabbing chest
pain), anxiety, dyspnoea and right ventricular enlargement
are exhibited. Massive occlusion causes severe pulmonary
hypertension, shock and sudden death.

E VA LUAT I O N A N D T R E AT M E N T
Routine chest x-rays and pulmonary function tests are not
definitive for pulmonary embolism. On chest x-rays, the
infarcted portion of the lung appears as a nonspecific
infiltrate in a classic wedge shape bordering the pleura.
Arterial blood gas analyses usually demonstrate hypoxaemia
and hyperventilation (leading to respiratory alkalosis). A
ventilation–perfusion scan, in which lungs are scanned after
injection and inhalation of a radioactive substance, may
indicate embolism (see Fig. 25.34). Today, the diagnosis is
made by measuring elevated levels of D-dimer in the blood
(an indicator of fibrinolysis) in combination with spiral CT
scanning.81

The ideal treatment for pulmonary embolism is
prevention through elimination of predisposing factors for
individuals at risk. Venous stasis in hospital patients is
minimised by leg elevation, bed exercises, position changes,
early postoperative ambulation and pneumatic calf
compression. Clot formation is also prevented by prophylactic
low-dose anticoagulant therapy usually with low-molecular-
weight heparin or warfarin.

Anticoagulant therapy is the primary treatment for
pulmonary embolism. Intravenous administration of heparin

dysfunction to severe and life-threatening changes in
ventilation/perfusion ratios.

Pulmonary embolism
Pulmonary embolism is occlusion of a portion of the
pulmonary vascular bed by an embolus (see Fig. 25.32),
which can be a thrombus (blood clot), tissue fragment,
lipids (fats), foreign body or an air bubble (air embolism).
More than 90% of pulmonary emboli result from clots
formed in the veins of the legs and pelvis.

Risk factors for pulmonary thromboembolism, or the
obstruction of a pulmonary vessel by a thrombus, include
conditions and disorders that promote blood clotting as a
result of venous stasis (slowing or stagnation of blood flow
through the veins), hypercoagulability (increased tendency
of the blood to form clots) and injuries to the endothelial
cells that line the vessels. No matter the source, a blood
clot becomes an embolus when all or part of it breaks away
from the site of formation and begins to travel in the
bloodstream. Thromboembolism or deep vein thrombus
is described further in Chapter 23.

Although the overall incidence of pulmonary embolism
has declined (2 per 1000 people per year), it remains an
important cause of death, especially in the elderly and
hospitalised individuals. Trauma, especially head injuries
and fractures of the lower extremities, spine or pelvis, confers
a high risk for venous thromboembolism.

PAT H O P HYS I O LO G Y
The impact or effect of the embolus depends on the extent
of pulmonary blood flow obstruction, the size of the affected
vessels, the nature of the embolus and the secondary effects.
Pulmonary emboli can occur as any of the following:
• massive occlusion: an embolus that occludes a major

portion of the pulmonary circulation (i.e. main
pulmonary artery embolus)

FIGURE 25.32

Pulmonary embolism.
Large pulmonary embolus (arrow) lying in the pulmonary artery
(retracted back for visualisation).

748 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

PAT H O P HYS I O LO G Y
Cor pulmonale develops as pulmonary hypertension and
creates chronic pressure overload in the right ventricle,
similar to that created in the left ventricle by systemic
hypertension. (Hypertension is discussed in Chapter 23.)
Pressure overload increases the work of the right ventricle
and first causes hypertrophy of the normally thin-walled
heart muscle, but eventually leads to dilation and failure
of the ventricle. Acute hypoxaemia, as with pneumonia,
can exaggerate pulmonary hypertension and dilate the
ventricle as well. The right ventricle usually fails when
pulmonary artery pressure equals systemic blood pressure.

is begun immediately and is followed by oral doses of
warfarin. Studies suggest that low-molecular-weight heparins
(e.g. enoxaparin) are as safe and effective as standard heparin
but are easier to administer.82 If a massive life-threatening
embolism occurs, a fibrinolytic agent is sometimes used
and some individuals will require surgical thrombectomy.

Cor pulmonale
Cor pulmonale consists of right ventricular enlargement
(hypertrophy or dilation, or both) and failure. It is most
commonly caused by pulmonary hypertension.

C
O
N
C
E
P
T
M

A
P Venous stasisVessel injury

Hypercoagulability
Predisposing factors

Predispose
e.g. DVT

dislogdes

causes
leads to
manifest as

Formation of thrombus
and occlusion of embolus

Conditions arising from
occlusion of pulmonary vasculature

Signs and symptoms of
pulmonary embolism

Thrombus formation

Portion of thrombus

Occlusion of part of pulmonary circulation

Hypoxic vasoconstriction
Decreased surfactant

Release of neurohumoral and in�ammatory substances

Pulmonary oedema

Atelectasis

Tachypnoea
Dyspnoea
Chest pain

Increased dead space
Ventilation–perfusion

imbalances
Decreased PaO2

Pulmonary infarction
Pulmonary hypertension

Decreased cardiac output
Systemic hypotension

Shock

FIGURE 25.33

The pathogenesis of massive pulmonary embolism caused by a thrombus (venous thromboembolism).
A thrombus can form in another vessel, usually a deep vein thrombosis in the leg. From this, a fragment can dislodge and travel
through the blood to the lungs, where it forms a pulmonary embolism. This blockage to the pulmonary vessel may lead to severe
complications including severe impairment of gas exchange, pulmonary oedema and hypertension, and shock.

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 749

C L I N I C A L MA N I F E S TAT I O N S
The clinical manifestations of cor pulmonale may be
obscured by primary respiratory disease and appear only
during exercise testing. The heart may appear normal at
rest, but with exercise, cardiac output falls. The
electrocardiogram may show right ventricular hypertrophy.
Increased pressures in the systemic venous circulation can
cause jugular venous distension, hepatosplenomegaly
(enlarged liver and spleen due to venous engorgement) and
peripheral oedema.

E VA LUAT I O N A N D T R E AT M E N T
Diagnosis is based on physical examination, radiological
examination, electrocardiogram and echocardiography. The
goal of treatment for cor pulmonale is to decrease the
workload of the right ventricle by lowering pulmonary
artery pressure. Treatment success depends on reversal of
the underlying lung disease.

F O C U S O N L E A R N I N G

1 Describe how thrombus formation can lead to pulmonary
embolism.

2 Describe cor pulmonale and the clinical manifestations.

alterations and their signs and symptoms. You should be
familiar with the diseases and now need to consolidate
your knowledge with an understanding of the clinical
manifestations that individuals with pulmonary system
alterations will exhibit.

Conditions caused
by pulmonary alterations
Pulmonary oedema
One of the most serious conditions resulting from alterations
to either the pulmonary system or the cardiovascular system
is pulmonary oedema. Simply, pulmonary oedema is excess
water in the lungs. The normal lungs are kept free from
excess water by lymphatic drainage and a balance among
capillary hydrostatic pressure, capillary oncotic pressure
and capillary permeability (see Chapter 22). In addition,
surfactant lining the alveoli repels water, keeping fluid from
entering the alveoli. Predisposing factors for pulmonary
oedema include heart disease, acute respiratory distress
syndrome and inhalation of toxic gases. The pathogenesis
of pulmonary oedema is shown in Fig. 25.35.

The most common cause of pulmonary oedema is heart
disease. When the left ventricle fails, filling pressures on
the left side of the heart increase and vascular volume
redistributes into the lungs, subsequently causing an increase
in pulmonary capillary hydrostatic pressure and a
back-tracking of excess fluid into the lungs. When the
hydrostatic pressure exceeds oncotic pressure (which holds
fluid in the capillary), fluid moves out into the interstitial
spaces (the spaces within the alveolar septum between the
alveolus and capillary). When the flow of fluid out of the
capillaries exceeds the lymphatic system’s ability to remove
it, pulmonary oedema develops.

A B

FIGURE 25.34

Ventilation–perfusion scan.
A Normal study with no defects visible. B Defects in scan showing lack of radioactive tracer uptake indicative of pulmonary embolism.

Clinical manifestations of
pulmonary alterations
So far in this chapter we have explored the pathophysiology
of the major pulmonary system disorders. In the following
sections we look at the manifestations of these disorders
— the conditions that result from pulmonary system

750 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

Another cause of pulmonary oedema is capillary injury
that increases capillary permeability, as in cases of acute
respiratory distress syndrome. Capillary injury causes water
and plasma proteins to leak out of the capillary and move
into the interstitial spaces, increasing interstitial oncotic
pressure, which is usually very low. As the interstitial oncotic
pressure begins to equal capillary oncotic pressure, water
moves out of the capillary and into the lungs. (This
phenomenon is discussed in Chapter 22).

Clinical manifestations of pulmonary oedema include
dyspnoea, hypoxaemia and increased work of breathing.
Patients may also experience orthopnoea and paroxysmal
nocturnal dyspnoea. Physical examination may reveal
inspiratory crackles and dullness to percussion over the
lung bases. In severe pulmonary oedema, pink frothy sputum
is expectorated (coughed up) and oxygen levels decrease,
while carbon dioxide levels increase, due to inadequate gas
exchange.

The mainstay of therapy is supplemental oxygen.
Individuals with pulmonary oedema usually require the
delivery of a higher concentration of oxygen. The treatment
of pulmonary oedema depends on its cause. If the oedema
is caused by increased hydrostatic pressure that results from
heart failure, therapy is geared towards improving cardiac
output with diuretics (to reduce fluid volume), vasodilators
(to redistribute blood to other areas of the body) and drugs
that improve the contraction of the heart muscle (to allow
normal blood flow throughout the systemic circulation).

If oedema is the result of increased capillary permeability
resulting from injury, the treatment is focused on removing
the offending agent and supportive therapy to maintain
adequate ventilation and circulation. When oxygen therapy
alone is inadequate to meet metabolic demand, positive-
pressure mechanical ventilation may be needed to improve
ventilation and oxygenation.

HYPOXAEMIA
Hypoxaemia, or reduced oxygenation of arterial blood
(reduced PaO2), is caused by respiratory alterations, whereas
hypoxia, or reduced oxygenation of cells in tissues, may be
caused by alterations of other systems as well. Although
hypoxaemia can lead to tissue hypoxia, tissue hypoxia can
result from other abnormalities unrelated to alterations of
pulmonary function, such as low cardiac output.83

Hypoxaemia results from problems with one or more
of the major mechanisms of oxygenation:
• oxygen delivery to the alveoli

a oxygen content of the inspired air
b ventilation of the alveoli

• diffusion of oxygen from the alveoli into the blood
a balance between alveolar ventilation and perfusion
b diffusion of oxygen across the alveolar–capillary

barrier
• perfusion of pulmonary capillaries.

C
O
N
C
E
P
T
M

A
P Valvular dysfunctionCoronary artery

disease
Left ventricular

dysfunction

Injury to capillary
endothelium

Blockage of
lymphatic vessels

Increased left
atrial pressure

can cause

leads to
leads to leads to

causes causes
results in
results in results in

Increased pulmonary
capillary hydrostatic

pressure
Pulmonary oedema

Movement of �uid and plasma
proteins from capillary to
interstitial space (alveolar

septum) and alveoli

Accumulation of �uid
in interstitial space

Inability to remove
excess �uid from
interstitial space

Increased capillary
permeability and

disruption of surfactant
production by alveoli

FIGURE 25.35

The pathogenesis of pulmonary oedema.
Pulmonary oedema can arise from increased pulmonary blood pressure, increased capillary permeability, or blockage of the lymphatic
drainage.

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 751

somewhat greater than ventilation in the lung bases and
because some blood is normally distributed to the bronchial
circulation. An abnormal ventilation/perfusion ratio is the
most common cause of hypoxaemia (see Fig. 25.36). This
is referred to as a ventilation–perfusion mismatch (clinically
abbreviated to V̇/Q̇ mismatch). Hypoxaemia can be caused
by inadequate ventilation of well-perfused areas of the lung
(low ventilation–perfusion). Mismatching of this type occurs
in atelectasis, in asthma as a result of bronchoconstriction
and in pulmonary oedema and pneumonia when alveoli
are filled with fluid. When blood passes through portions
of the pulmonary capillary bed that receive no ventilation,
blood is not oxygenated, resulting in hypoxaemia.
Hypoxaemia can also be caused by poor perfusion of
well-ventilated portions of the lung (high ventilation–
perfusion), resulting in wasted ventilation. The most
common cause of high ventilation–perfusion mismatching
is a pulmonary embolus that impairs blood flow to a segment
of the lung. An area where alveoli are ventilated but not
perfused is termed alveolar dead space.

The second factor affecting diffusion of oxygen from
the alveoli into the blood is the alveolar–capillary barrier.
Diffusion of oxygen through the alveolar–capillary membrane
is impaired if the membrane is thickened or the surface

The amount of oxygen in the alveoli is dependent on
two factors. The first factor is the presence of adequate
oxygen content in the inspired air. The amount of oxygen
in inspired air is expressed as the percentage or fraction of
air that is composed of oxygen. Anything that decreases
the oxygen content of inspired air (such as high altitude)
decreases oxygen in the alveoli. The second factor is the
amount of alveolar minute volume (see Chapter 24 for
alveolar ventilation). Hypoventilation results in an increased
alveolar carbon dioxide and decreased oxygen such that
diffusion across the alveoli is impacted. This type of
hypoxaemia can be completely corrected if alveolar
ventilation is improved by increasing the rate and depth
of breathing. Hypoventilation causes hypoxaemia in
unconscious individuals; in those with neurological,
muscular or bone diseases that restrict chest expansion;
and in individuals who have COPD.

Diffusion of oxygen from the alveoli into the blood is
also dependent on two factors. The first is the balance
between the amount of air getting into the alveoli and the
amount of blood perfusing the capillaries around the alveoli.
Normally, alveolar capillary lung units receive almost equal
amounts of ventilation and perfusion. The normal
ventilation/perfusion ratio is 0.8 : 0.9 because perfusion is

Airway Impaired
ventilation

Hypoxaemia

Hypoxaemia Hypoxaemia

From
pulmonary artery

Alveolocapillary
membrane

Alveolus

To
pulmonary vein

Normal ventilation–perfusion Low ventilation–perfusion

Shunt (very low)
ventilation–perfusion

High ventilation–perfusion

Blocked ventilation

Collapsed
alveolus

Alveolar
dead space

Impaired perfusion

FIGURE 25.36

Ventilation–perfusion abnormalities.
Normal ventilation–perfusion occurs when ventilation and perfusion are both ideal at the alveoli. Low ventilation–perfusion occurs due to
impairments in ventilation. High ventilation–perfusion occurs due to impairments in perfusion.

752 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

2 Absorption atelectasis results from removal of air from
obstructed or hypoventilated alveoli or from inhalation
of concentrated oxygen or anaesthetic agents (see Fig.
25.37).
Clinical manifestations of atelectasis are similar to those

of pulmonary infection including dyspnoea, cough and
fever.

Atelectasis tends to occur after surgery. Postoperative
patients may have received supplemental oxygen or
inhaled anaesthetics and they are usually in pain, shallow
breathe, are reluctant to change position and produce thick
secretions that tend to pool in dependent portions of the
lungs. Prevention and treatment of postoperative atelectasis
usually include deep breathing, frequent position changes
and early ambulation. Deep breathing opens connections
between patent and collapsed alveoli, called pores of Kohn.
This allows air to flow into the collapsed alveoli (collateral
ventilation) and aids in the expulsion of intrabronchial
obstructions.

Pneumothorax
Pneumothorax is the presence of air or gas in the pleural
space caused by a rupture in the visceral pleura (which
surrounds the lungs) or the parietal pleura and chest wall.
As air separates the visceral and parietal pleurae, it destroys
the negative pressure of the pleural space and disrupts the
equilibrium between the elastic recoil forces of the lung
and chest wall. The lung then tends to recoil by collapsing
towards the hilum (see Fig. 25.38).

Pneumothorax can occur spontaneously or secondary
to trauma. The most common presentation of spontaneous
pneumothorax occurs unexpectedly in healthy males aged
20–40 years. Secondary pneumothorax can result from rib
fractures, COPD or chest stabbings or shootings.

area available for diffusion is decreased. Thickened alveolar–
capillary membranes, as occur with oedema (tissue swelling)
and fibrosis (formation of fibrous lesions), increase the time
required for oxygen to diffuse from the alveoli into the
capillaries. If diffusion is slowed enough, the oxygen in the
alveoli and capillary blood do not have time to equilibrate
and hence oxygenation of the blood is limited.

Hypercapnia
Hypercapnia, or increased carbon dioxide in the arterial
blood, is caused by hypoventilation of the alveoli. As
discussed in Chapter 24, carbon dioxide is easily diffused
from the blood into the alveolar space; thus, minute volume
(ventilation rate × tidal volume) determines not only alveolar
ventilation but also carbon dioxide levels in the blood.

There are many causes of hypercapnia. Most are a result
of decreased drive to breathe or an inadequate ability to
respond to ventilatory stimulation. Some of these causes
include: (1) depression of the respiratory centre in the
brainstem by drugs such as morphine and heroin; (2)
diseases of the medulla, including infections of the central
nervous system or trauma; (3) abnormalities of the spinal
conducting pathways, as in spinal cord disruption; (4)
diseases of the neuromuscular junction or of the respiratory
muscles themselves, as in myasthenia gravis or muscular
dystrophy; (5) thoracic cage abnormalities, as in chest injury
or congenital deformity; (6) large airway obstruction, as
in tumours or sleep apnoea; and (7) increased work of
breathing or physiological dead space, as in emphysema.

Acute respiratory failure
Respiratory failure is defined as inadequate gas exchange
such that arterial oxygen levels are less than 50 mmHg or
arterial carbon dioxide levels are greater than 50 mmHg
with pH less than 7.25. Respiratory failure can result from
direct injury to the lungs, airways or chest wall, or indirectly
because of injury to another body system, such as the brain
or spinal cord. It can occur in individuals who have an
otherwise normal pulmonary system or in those with
underlying chronic pulmonary disease. Most pulmonary
diseases can cause episodes of acute respiratory failure. If
the respiratory failure is primarily hypercapnic (i.e. due to
high carbon dioxide levels), it is the result of inadequate
alveolar ventilation. If the respiratory failure is primarily
hypoxaemic (i.e. due to low oxygen levels), it is the result
of inadequate exchange of oxygen between the alveoli and
the capillaries. Many individuals will have combined
hypercapnic and hypoxaemic respiratory failure.

Atelectasis
Atelectasis is the collapse of lung tissue. It can occur due
to lack of lung expansion, such as that experienced after
surgery. There are two types of atelectasis:
1 Compression atelectasis is caused by external pressure

exerted by tumour, fluid or air in pleural space or by
abdominal distension pressing on a portion of lung,
causing alveoli to collapse.

Absorption Compression

FIGURE 25.37

Different forms of atelectasis.
Lung collapse can occur by absorption, usually from decreased air
flow through the lung, or from compression from outside of the
lung.

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 753

re-expands and the pleural rupture is healed, the chest tube is
removed.

Pleural effusion
Pleural effusion is the presence of excess fluid in the
pleural space. The most common mechanism of pleural
effusion is migration of fluids and other blood components
through the walls of intact capillaries bordering the pleura.
Pleural effusions that enter the pleural space from the intact
blood vessels can be transudative (watery) or exudative
(high in concentrations of white blood cells and plasma
proteins). Mechanisms of pleural effusion are summarised in
Table 25.6.

Small collections of fluid normally can be drained away
by the lymphatics. Dyspnoea, compression atelectasis with
impaired ventilation and mediastinal shift occur with large
effusions. Pleural pain is present if the pleura are inflamed
and cardiovascular manifestations occur in a large, rapidly
developing effusion.

Diagnosis is confirmed by chest x-ray (see Fig. 25.39)
and thoracentesis (needle aspiration), which can determine
the type of effusion and provide symptomatic relief. If the
effusion is large, drainage usually requires the placement
of a chest tube.

Empyema
Empyema (infected pleural effusion) is the presence of pus
in the pleural space. It is thought to develop when the
pulmonary lymphatics become blocked, leading to an
outpouring of contaminated lymphatic fluid into the pleural
space. Empyema occurs most commonly in older adults

Both spontaneous and secondary pneumothorax can
present as either open or tension. In open pneumothorax,
air pressure in the pleural space equals barometric
pressure because air that is drawn into the pleural space
during inspiration (through the damaged chest wall and
parietal pleura or through the lungs and damaged visceral
pleura) is forced back out during expiration. In tension
pneumothorax, however, the site of pleural rupture acts as
a one-way valve, permitting air to enter on inspiration but
preventing its escape by closing up during expiration. As
more and more air enters the pleural space, air pressure in
the pneumothorax begins to exceed barometric pressure.
Tension pneumothorax is life-threatening. Air pressure
in the pleural space pushes against the already recoiled
lung, causing compression atelectasis and against the
mediastinum, compressing and displacing the heart and great
vessels.

Clinical manifestations of spontaneous or secondary
pneumothorax begin with sudden pleural pain, tachypnoea
and dyspnoea (rapid breathing and difficulty breathing,
respectively). The manifestations depend on the size of the
pneumothorax. Physical examination may reveal absent
or decreased breath sounds. Tension pneumothorax may
be complicated by severe hypoxaemia, tracheal deviation
away from the affected lung and hypotension (low blood
pressure). Deterioration occurs rapidly and immediate
treatment is required. Diagnosis of pneumothorax is
made with chest x-rays and CT scans. Pneumothorax
is treated with insertion of a chest tube that is attached
to a water-seal drainage system with suction, such that
negative pressure is restored. After the pneumothorax

Normal
lung

Chest
wall

Pleural
space

Diaphragm

Mediastinum

Outside air enters
because of disruption
of chest wall and
parietal pleura

Lung air enters
because of disruption
of visceral pleura

FIGURE 25.38

Pneumothorax.
Air in the pleural space causes the lung to collapse around the hilus and may push mediastinal contents (heart and great vessels) towards
the other lung.

754 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

1 and 3 years or in individuals whose normal swallowing
mechanism and cough reflex are impaired by central or
peripheral nervous system abnormalities. Predisposing
factors include an altered level of consciousness caused by
substance abuse, sedation or anaesthesia; seizure disorders;
cerebrovascular accident; and neuromuscular disorders that
cause dysphagia (see Chapter 27). The right lung, particularly
the right lower lobe, is more susceptible to aspiration than
the left lung because the branching angle of the right main
stem bronchus is straighter than the branching angle of
the left main stem bronchus (see Chapter 24).

Foreign bodies lodged in the larynx or upper trachea
cause cough, stridor, hoarseness or inability to speak,
respiratory distress and agitation or panic. The presentation
is often dramatic and frightening.

Aspiration of acidic gastric fluid (pH of less than 2.5)
may cause lung inflammation. Bronchial damage includes
inflammation, loss of ciliary function and bronchospasm.
In the alveoli, acidic gastric fluid damages the alveolar–
capillary membrane, allowing plasma and blood cells to
move from the capillaries into the alveoli. The lung becomes
stiff and non-compliant as surfactant production is disrupted,
leading to further oedema and collapse.

Preventive measures for individuals at risk are more
effective than treatment of known aspiration. The most
important preventive measures include the semi-recumbent
position, the surveillance of enteral feeding and the
avoidance of excessive sedation. Nasogastric tubes, which
are often used to remove stomach contents, are used to
prevent aspiration but can also cause aspiration if fluid
and particulate matter are regurgitated as the tube is being
placed.

Treatment of aspiration of foreign bodies may include
bronchoscopy to remove the foreign body, if sneezing and
coughing does not displace the object. More serious
aspirations with either stomach contents or ingestion of

and children and usually develops as a complication of
pneumonia, surgery, trauma or bronchial obstruction from
a tumour.

Individuals with empyema present clinically with
cyanosis, fever, tachycardia (rapid heart rate), cough and
pleural pain. Diagnosis is made by chest x-rays, thoracentesis
and sputum culture.

The treatment for empyema includes the administration
of appropriate antimicrobials and drainage of the pleural
space with a chest tube.

Aspiration
Aspiration is the inhalation of fluid and solid particles into
the lung. It tends to occur in children between the ages of

TABLE 25.6 Mechanisms of pleural effusion

TYPE OF FLUID/
EFFUSION SOURCE OF ACCUMULATION PRIMARY OR ASSOCIATED DISORDER

Transudate
(hydrothorax)

Watery fluid that diffuses out of capillaries
beneath the pleura (i.e. capillaries in the lungs or
chest wall)

Cardiovascular disease that causes high pulmonary
capillary pressures; liver or kidney disease that disrupts
plasma protein production, causing hypoproteinaemia
(decreased oncotic pressure in the blood vessels)

Exudate Fluid rich in cells and proteins (leucocytes, plasma
proteins of all kinds; see Chapter 13) that migrates
out of the capillaries

Infection, inflammation or malignancy of the pleura that
stimulates mast cells to release biochemical mediators
that increase capillary permeability

Pus (empyema) Debris of infection (microorganisms, leucocytes,
cellular debris) dumped into the pleural space by
blocked lymphatic vessels

Pulmonary infections, such as pneumonia; lung
abscesses; infected wounds

Blood
(haemothorax)

Haemorrhage into the pleural space Traumatic injury, surgery, rupture or malignancy that
damages blood vessels

Chyle (chylothorax) Chyle (milky fluid containing lymph and fat
droplets) that is dumped by lymphatic vessels
into the pleural space instead of passing from the
gastrointestinal tract to the thoracic duct

Traumatic injury, infection or disorder that disrupts
lymphatic transport

FIGURE 25.39

Chest x-ray of a right-side pleural effusion.
Note the arrows highlighting the extent of the effusion. This angle
should be sharp and this blunting is due to fluid formation.

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 755

Dyspnoea can occur transiently or can become chronic.
One cause of dyspnoea is pulmonary congestion usually
resulting from heart disease. Pulmonary congestion tends
to cause dyspnoea when the individual is lying down
(orthopnoea). The horizontal position redistributes body
water, causes the abdominal contents to exert pressure on
the diaphragm and decreases the efficiency of the respiratory
muscles. Sitting up in a forward-leaning posture or
supporting the upper body on several pillows generally
relieves orthopnoea. Some individuals with pulmonary or
cardiac disease wake up at night gasping for air and have
to sit up or stand to relieve the dyspnoea (paroxysmal
nocturnal dyspnoea).

Cough
A cough is a protective reflex that cleanses the lower airways
by an explosive expiration. Inhaled particles, accumulated
mucus, inflammation or the presence of a foreign body
initiates the cough reflex by stimulating the irritant receptors
in the airways. There are only few of these receptors in the
most distal bronchi and the alveoli, thus it is possible for
significant amounts of secretions to accumulate in the distal
respiratory tree without cough being initiated. The cough
consists of inspiration, closure of the glottis and vocal cords,
contraction of the expiratory muscles and reopening of the
glottis, causing a sudden, forceful expiration that removes
the offending matter. The effectiveness of the cough depends
on the depth of the inspiration and the degree to which
the airways narrow, increasing the velocity of expiratory
gas flow.

Acute cough is cough that resolves within 2–4 weeks
of the onset of illness or resolves with treatment of the
underlying condition. It is most commonly the result of
upper respiratory infections, acute bronchitis, pneumonia,
heart failure, pulmonary embolus or aspiration.

Chronic cough is defined as cough that has persisted
for more than 4 weeks in children and 8 weeks in adults.
In non-smoking adults, the most common cause of chronic
cough is rhinosinusitis, asthma or gastro-oesophageal reflux
disease, in children it is asthma and protracted bacterial
bronchitis.88,89 In smokers, chronic bronchitis is the most
common cause of cough, although lung cancer must always
be considered. Approximately 5–10% of Australians suffer
from chronic cough and 20% of patients who take
angiotensin-converting enzyme (ACE) inhibitors (see
Chapter 23) develop a persistent dry cough, with some
patients experiencing severe cough that requires the drug
to be discontinued.

Management of chronic cough involves addressing the
common issues of environmental exposures and the concerns
of the patient and parents, then the institution of specific
therapy.88,90

Hypoventilation and hyperventilation
Hypoventilation is inadequate alveolar ventilation in relation
to metabolic demand. Hypoventilation occurs when minute
volume (tidal volume × ventilatory rate) is reduced. It is

solids or fluids into the lungs may necessitate supplemental
oxygen, mechanical ventilation, fluid restriction and steroids.
Bacterial pneumonia may develop as a complication of
aspiration and must be treated with broad-spectrum
antimicrobials.

F O C U S O N L E A R N I N G

1 Describe pulmonary oedema and list two causes.

2 Discuss the mechanisms that produce hypoxaemia and
hypercapnia.

3 Differentiate the different levels of hypoxaemia and
hypercapnia in acute respiratory failure.

4 Compare and contrast the two forms of atelectasis.

5 Compare and contrast open and tension pneumothorax.

6 Describe how pneumothorax differs from pleural effusion.

7 List causes of empyema.

8 Provide a list of 5 different causes of aspiration.

Signs and symptoms of
pulmonary alterations
Dyspnoea
Dyspnoea is the subjective sensation of uncomfortable
breathing, the feeling of not being able to get enough air.
It is often described as breathlessness, air hunger, shortness
of breath and laboured breathing. Everyone experiences
dyspnoea at some stage. One of the most common
non-pathological reasons is when you exercise heavily and
become short of breath — that is dyspnoea. Our discussion
here concerns dyspnoea that occurs at rest and is due to
pulmonary system pathophysiology.

Dyspnoea can be caused by many pulmonary disorders.
Disturbances of ventilation, gas exchange or ventilation–
perfusion relationships can cause dyspnoea, as can increased
work of breathing or any disease that damages lung tissue.
One proposed mechanism for dyspnoea is a mismatch
between sensory and motor input from the respiratory
centre in the brainstem such that there is more urge to
breathe than there is response by the respiratory muscles.
Other causes of dyspnoea include stimulation of central
and peripheral chemoreceptors and stimulation of afferent
receptors in the lungs and chest wall.

The signs of dyspnoea include flaring of the nostrils,
use of accessory muscles of ventilation and retraction
(pulling back) of the intercostal spaces. In dyspnoea caused
by lung tissue disease (e.g. pneumonia), retractions of tissue
between the ribs may be observed, although retractions
are more common in children than in adults. Dyspnoea
can be quantified using scales (such as the Borg Dyspnoea
Scale,84 the Medical Research Council (MRC) Dyspnoea
Score85 and the Dyspnoea-12)86 and is frequently associated
with significant anxiety.87

756 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

the brainstem is also a contributing factor. Cheyne-
Stokes breathing indicates that severe pathophysiological
disturbances have occurred and often is present immediately
before death.

Haemoptysis
Haemoptysis is the coughing up of blood or bloody
secretions. This should not be confused with haematemesis,
which is the vomiting of blood. Blood that is coughed up
is usually bright red, has an alkaline pH and may be mixed
with frothy sputum, whereas blood that is vomited is dark,
has an acidic pH and is mixed with food particles. However,
both are serious conditions.

Haemoptysis indicates a localised abnormality, usually
infection or inflammation that damages the bronchi, such
as bronchiectasis, or the lung tissue, such as tuberculosis
and cancer. Bronchoscopy, combined with chest CT scans,
is used to confirm the site of bleeding.

Cyanosis
Cyanosis is a bluish discolouration of the skin and mucous
membranes caused by increasing amounts of desaturated
or reduced haemoglobin (which is bluish) in the blood. It
generally develops when 5 g of haemoglobin is desaturated,
regardless of haemoglobin concentration.

Cyanosis can be caused by decreased arterial oxygenation,
ventilation–perfusion inequalities, decreased cardiac output,
a cold environment or anxiety. In adults, cyanosis is not
evident until severe hypoxaemia is present and therefore
is an insensitive indication of respiratory failure. Severe
anaemia (inadequate haemoglobin concentration) can cause
inadequate oxygenation of tissues without causing cyanosis.
However, individuals with polycythaemia (an abnormal
increase in the numbers of red blood cells) may have cyanosis
when oxygenation is adequate. Therefore, cyanosis must
be interpreted in relation to the underlying pathophysiology.
If cyanosis is suggested, the oxygen levels in the blood
should be measured. Central cyanosis (decreased oxygen
saturation of haemoglobin in arterial blood) is best seen
in buccal (cheek) mucous membranes and lips. Peripheral
cyanosis (slow blood circulation in fingers and toes) is best
seen in nail beds.

caused by alterations in pulmonary mechanics or in the
neurological control of breathing. When alveolar ventilation
is normal, carbon dioxide is removed from the lungs at the
same rate as that produced by cellular metabolism; therefore,
arterial and alveolar carbon dioxide values remain at normal
levels (between 35 and 45 mmHg). With hypoventilation,
carbon dioxide removal does not keep up with carbon
dioxide production and the level of carbon dioxide in the
arterial blood increases, causing hypercapnia (a carbon
dioxide level more than 45 mmHg). This results in respiratory
acidosis (pH less than 7.35), which can affect the function
of many tissues throughout the body. Blood gas analysis
(i.e. measurement of the arterial carbon dioxide level) reveals
hypoventilation.

Hyperventilation is alveolar ventilation exceeding
metabolic demands. The lungs remove carbon dioxide faster
than it is produced by cellular metabolism, resulting in
decreased carbon dioxide levels in the blood, or hypocapnia
(a carbon dioxide level less than 35 mmHg). Hypocapnia
results in respiratory alkalosis (pH greater than 7.45), which
also can interfere with tissue function. Like hypoventilation,
hyperventilation can be determined by arterial blood gas
analysis. Increased respiratory rate or tidal volume can occur
with severe anxiety, acute head injury, pain and in response
to conditions that cause insufficient oxygenation of the
blood.

Abnormal breathing patterns
Normal breathing (eupnoea) is rhythmic and effortless.
The resting ventilatory rate in adults is usually between 8
and 16 breaths per minute and tidal volume (the amount
of air in each breath) ranges from 400–800 mL. A short
expiratory pause occurs with each breath and the expiratory
phase is longer than inspiration, usually in a ratio of 1:2
(for inspiration time: expiration time). Disease states can
alter this ratio.

Laboured breathing occurs whenever there is an increased
work of breathing, especially if the airways are obstructed.
If the large airways are obstructed, a slow ventilatory rate,
large tidal volume, increased effort, prolonged inspiration
and expiration, and stridor or audible wheezing (depending
on the site of obstruction) are typical. In small airway
obstruction like that seen in asthma and COPD, a rapid
ventilatory rate, small tidal volume, increased effort and
prolonged expiration are often present.

Strenuous exercise or metabolic acidosis induces
Kussmaul breathing (slow deep breathing), or hyperpnoea
(excessive breathing), which is characterised by an increased
ventilatory rate, very large tidal volumes and no expiratory
pause. Another abnormal breathing pattern is Cheyne-Stokes
breathing, characterised by alternating periods of deep
and shallow breathing. Apnoea lasting from 15 to 60
seconds is followed by breaths that increase in volume
until a peak is reached; then breathing decreases again to
apnoea. Cheyne-Stokes breathing results from any condition
that slows the blood flow to the brainstem, which in turn
slows impulses sending information to the respiratory
centres of the brainstem. Neurological impairment above

F O C U S O N L E A R N I N G

1 List the primary signs and symptoms of pulmonary
disease.

2 Discuss reasons why individuals may experience dyspnoea.

3 Differentiate between acute and chronic cough.

4 Differentiate between hypoventilation and
hyperventilation.

5 Indicate reasons for haemoptysis.

6 Describe causes of cyanosis.

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 757

chapter SUMMARY

Disorders of the pulmonary system
• Obstructive airway diseases are characterised by

airway obstruction. Obstructive airway diseases can be
acute or chronic in nature and include asthma and
COPD.

• In asthma, the mechanisms causing airway obstruction
include bronchoconstriction, bronchial inflammation,
mucosal oedema and increased mucus production.

• Asthma control severity and control are used to
determine therapy.

• Asthma is a common and important problem in children,
adults and the elderly. Its origins are multifactorial,
including genetic, allergic and viral-triggered
mechanisms. Effective management is aimed at
decreasing chronic inflammation in the lungs,
eliminating known triggers from the environment, and
early recognition and treatment of acute symptoms. Best
practice asthma management includes effective
pharmacotherapy, self-management education, the
provision of a written asthma action plan and regular
medical review.

• Childhood asthma is best classified by clinical patterns to
support the spirometry results; different patterns of
wheezing may be observed. Childhood asthma may be
infrequent, frequent or persistent that progresses into
adulthood. Viral infections are common triggers for
childhood asthma.

• Chronic obstructive pulmonary disease (COPD) is an
obstructive airway disease which involves the occurrence
and the coexistence of chronic bronchitis and
emphysema. Asthma COPD overlap is common
particularly in older populations.

• COPD is an important cause of hypoxaemic and
hypercapnic respiratory failure.

• Chronic bronchitis causes airway obstruction resulting
from bronchial smooth muscle hypertrophy and
production of thick, tenacious mucus.

• In emphysema, destruction of the alveolar septa and loss
of passive elastic recoil lead to airway collapse and
obstruct gas flow during expiration.

• Acute respiratory distress syndrome results from an
acute diffuse injury to the alveolar–capillary membrane
and decreased surfactant production, which increases
membrane permeability and causes oedema and
atelectasis. There is progressive respiratory distress with
severe hypoxaemia and respiratory failure.

• Inhalation of noxious gases or prolonged exposure to
high concentrations of oxygen can damage the
bronchial mucosa or alveolar–capillary membrane and
cause inflammation or acute respiratory failure.

• Pneumoconiosis, which is caused by inhalation of dust
particles in the workplace, can cause pulmonary fibrosis,
susceptibility to lower airway infection and cancers.

• Cystic fibrosis is an autosomal recessive genetic disease
that affects many organ systems, especially the lungs
and digestive system. Airway secretions are particularly
thick and tenacious and the airways develop chronic
bacterial infection with pathogens such as Pseudomonas
aeruginosa and Staphylococcus aureus. Chronic infection,
plugged airways and severe inflammation cause long-
term lung damage and ultimately death. However, the
prognosis is improving and most patients with cystic
fibrosis now survive to adulthood.

• Bronchiectasis is an abnormal permanent dilation and
distortion of the bronchi and bronchioles, resulting from
chronic inflammation of the airways, and leading to
progressive destruction of the bronchial walls and lung
tissue.

Infections of the pulmonary system
• Upper respiratory tract infections are the most common

cause of short-term disability in Australia and New
Zealand.

• Serious lower respiratory tract infections occur most
often in the elderly and in individuals with impaired
immunity or underlying disease.

• Viral pneumonia can be severe, but is more often an
acute self-limiting lung infection usually caused by the
influenza virus.

• Tuberculosis is a lung infection caused by Mycobacterium
tuberculosis.

• In tuberculosis, the inflammatory response proceeds to
isolate colonies of bacterium by enclosing them in
tubercles and surrounding the tubercles with scar tissue.
These may remain dormant within the tubercles for life
or, if the immune system breaks down, cause recurrence
of active disease.

• Influenza is a common viral infection that affects large
proportions of the population. This form is seasonal;
however, more pathogenic forms of influenza involving
mutations with avian and swine influenza have infected
humans and may cause serious pandemics in the future.

Paediatrics and pulmonary infections
• Bronchiolitis is the inflammatory obstruction of small

airways. It is most common in children.

Lung cancer
• Lung cancer, the most common cause of cancer death in

Australia and New Zealand, is commonly caused by
cigarette smoking.

758 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

• Cancer cell types include non-small cell carcinoma
(squamous cell, adenocarcinoma and large cell) and
small cell carcinoma. Each type arises in a characteristic
site or type of tissue, causes distinctive clinical
manifestations and differs in likelihood of metastasis and
prognosis.

Obstructive sleep apnoea
• Obstructive sleep apnoea syndrome is defined by partial

or complete upper airway obstruction during sleep with
disruption of normal ventilation and normal sleep
patterns. It affects a large percentage of adult males
(typically middle-aged and older) and children.

• Risk factors for adults are obesity, age, smoking and
gender; in children the most common cause is
adenotonsillar hypertrophy.

Paediatrics and pulmonary disorders
• Croup is an acute respiratory illness of young children,

usually caused by parainfluenza virus. This infection
causes swelling of the upper trachea. The typical sign is a
seal-like barking cough, which appears after a few days
of rhinorrhoea, sore throat and low-grade fever.

• Respiratory distress syndrome of the newborn usually
occurs in premature infants who are born before
surfactant production and alveolar capillary
development are complete. Atelectasis and
hypoventilation cause hypoxaemia and hypercapnia.
Prenatal steroids and postnatal surfactant are beneficial
therapies.

• Sudden infant death syndrome (SIDS) is the leading
cause of postnatal death for infants outside of the
hospital setting and is associated with low birth weight,
a prone sleeping position and other environmental
factors. Some risk factors are modifiable — the prime
example is the profound reduction in SIDS since
widespread adoption of recommendations for supine
positioning of infants during sleep.

Alterations of pulmonary blood flow
and pressure
• Pulmonary vascular diseases are caused by embolism or

hypertension in the pulmonary circulation.
• Pulmonary embolism is occlusion of a portion of the

pulmonary vascular bed by a thrombus (most common),
tissue fragment or air bubble. Depending on its size and
location, the embolus can cause hypoxic
vasoconstriction, pulmonary oedema, atelectasis,
pulmonary hypertension, shock and even death.

• Cor pulmonale is right ventricular enlargement caused
by chronic pulmonary hypertension. Cor pulmonale
progresses to right ventricular failure if the pulmonary
hypertension is not reversed.

Clinical manifestations of pulmonary alterations
• Pulmonary oedema is excess water in the lungs caused

by disturbances of capillary hydrostatic pressure,

capillary oncotic pressure or capillary permeability. A
common cause is left heart failure, which increases the
hydrostatic pressure in the pulmonary circulation.

• Hypoxaemia is a reduced oxygen level in the blood
caused by (1) decreased oxygen content of inspired gas,
(2) hypoventilation, (3) diffusion abnormality or (4)
ventilation–perfusion mismatch.

• Hypercapnia is an increased carbon dioxide level in the
blood caused by hypoventilation.

• Atelectasis is the collapse of alveoli resulting from
compression of lung tissue or absorption of gas from
obstructed alveoli.

• Pneumothorax is the accumulation of air in the pleural
space. It can be caused by spontaneous rupture of
weakened pleural areas or it can be secondary to pleural
damage caused by disease or trauma.

• Pneumothorax can be open, which means that the lung
only partially collapses, or tension, which means that
pressure builds up in the pleural space and can
compress both the affected lung and the mediastinum.

• Pleural effusion is the accumulation of fluid in the pleural
space, usually resulting from disorders that promote
transudation or exudation from capillaries underlying
the pleura but occasionally resulting from blockage or
injury that causes lymphatic vessels to drain into the
pleural space.

• Empyema (infected pleural effusion) is the presence of
pus in the pleural space.

• Dyspnoea is the feeling of breathlessness and increased
respiratory effort. It is a common pulmonary disorder
symptom.

• Coughing is a protective reflex that expels secretions and
irritants from the lower airways.

• Hypoventilation is decreased alveolar ventilation caused
by airway obstruction, chest wall restriction or altered
neurological control of breathing. Hypoventilation
causes increased carbon dioxide levels.

• Hyperventilation is increased alveolar ventilation
produced by anxiety, head injury or severe hypoxaemia.
Hyperventilation causes decreased carbon dioxide levels.

• Abnormal breathing patterns are adjustments made by
the body to minimise the work of the respiratory
muscles. They include Kussmaul and Cheyne-Stokes
breathing.

• Haemoptysis is expectoration of bloody mucus, which
can be caused by bronchitis, tuberculosis, abscess,
neoplasms and other conditions that cause
haemorrhage from damaged vessels.

• Cyanosis is a bluish discolouration of the skin caused by
desaturation of haemoglobin, polycythaemia or
peripheral vasoconstriction.

CHAPTER 25 AlTeRATIOnS Of PulmOnARy funCTIOn ACROSS The lIfe SPAn 759

A D U L T
Craig is 57 years old and has just been diagnosed with
squamous cell lung cancer. Although he admits that he was
well aware that lung cancer was a risk of smoking, he was not
expecting such devastating news until he was much older.
A large growth was found in the left primary bronchus, and
metastasis has already occurred to another location within the
lung tissue. His symptoms include cough and haemoptysis; it
was haemoptysis which led to his diagnosis of cancer.

1 Compare the main features of the different types of lung
cancer.

2 Explain the likely clinical progression of Craig’s condition.
3 Describe the relationship between cigarette smoking and

the p53 gene.
4 Discuss the potential reasons for encouraging Craig to

quit smoking, given that he already has lung cancer.
5 Lung cancer has a very high incidence and mortality in

Australia and New Zealand. Outline possible reasons why
we do not have national lung cancer screening programs
in our countries.

CASE STUDY

A G E I N G
John is 73 years old with COPD. He is prescribed tiotropium
bromide daily and salbutamol 2 puffs as required. He uses
his salbutamol several times per day and his tiotropium as
prescribed. His wife died 5 years ago and since then he has not
been taking care of himself very well; he is no longer active
and doesn’t like to go out too much.
He presented to hospital with his daughter as she was
concerned about him. She states that over the last 8 days he
has experienced an increase in his symptoms; he had a fever,
was increasingly breathless, and was coughing up green
phlegm. She states that he had been increasingly irritable
and not attending to his meals or personal care as he was too
breathless. He had seen his doctor 4 days ago who had started
oral amoxicillin for 7 days and had advised him to return if
it did not get any better. The doctor also indicated that he
should return once he was better for his influenza vaccine.
She reported that this was the third time in the last 12 months
that she needed to take her dad to the doctor or emergency
department because of a flare-up of his breathing.
Physical examination revealed decreased breath sounds
throughout both lung fields with bibasal crackles, tachypnoea

(ventilatory rate: 32 breaths per minute) with accessory muscle
use, temperature 37.9°C, pursed lip breathing, tachycardia
(heart rate: 116 beats per minute), oxygen saturations of 84%
and anxiety. Spirometry was performed in the emergency
department; his FEV1was 44% of predicted, his FVC was 106%
of predicted and his FEV1/VC ratio was 0.41.
An urgent arterial blood gas was performed, which revealed
mild hypercapnia PaCO2 (48 mmHg pH 7.35) and hypoxaemia
(PaO2 78 mmHg). Oxygen prongs were applied at a flow of 2 L/
min and he was administered prednisolone and salbutamol
via the pressurised metered dose inhaler and large volume
spacer.
1 Describe the most probable reasons for John’s acute

exacerbation.
2 Describe why the arterial blood gas revealed respiratory

acidosis as it relates to COPD.
3 Explain the results of his spirometry test and the

implications of these results.
4 Based on the history discuss the impact of his previous

exacerbations.
5 Differentiate between the pathophysiology of upper

respiratory tract infections and asthma.

CASE STUDY
Downloaded for dikshya kharel (dikshyakharels@gmail.com) at Western Sydney University from ClinicalKey.com.au/nursing by Elsevier
on April 23, 2021. For personal use only. No other uses without permission. Copyright ©2021. Elsevier Inc. All rights reserved.

760 PART 4 AlTeRATIOnS TO bOdy mAInTenAnCe

1 Using changes in airflow characteristics, differentiate
between obstructive and restrictive lung diseases.

2 Describe how smoking affects pulmonary function
and how it contributes to the development of chronic
obstructive pulmonary disease.

3 Differentiate between an upper respiratory tract infection
and a lower respiratory tract infection. Provide examples to
supplement your answer.

4 Compare the different types of bronchogenic lung cancer
and the signs and symptoms that arise.

5 Provide a pathophysiological outline of the development of
obstructive sleep apnoea.

6 Explain the pathogenesis of cystic fibrosis and why
individuals develop clinical manifestations in other body
systems.

7 Explain why pulmonary embolism is a potentially fatal
condition.

8 Discuss how pulmonary oedema can arise and what
treatment options are available.

9 Provide explanations outlining the differences between
pneumothorax, pleural effusion and empyema.

10 Suggest why dyspnoea and cough are common symptoms
of many pulmonary conditions.

REVIEW QUESTIONS

25 Alterations of pulmonary function across the life span

Chapter outline
Key terms
Introduction
Disorders of the pulmonary system
Obstructive airway diseases
Asthma
Pathophysiology
Clinical manifestations
Evaluation and treatment
Chronic obstructive pulmonary disease
Chronic bronchitis
Pathophysiology
Emphysema
Pathophysiology
Clinical manifestations of COPD
Evaluation and management of COPD
Cystic fibrosis
Pathophysiology
Clinical manifestations
Evaluation and treatment
Bronchiectasis

Restrictive airway diseases
Acute respiratory distress syndrome
Pathophysiology
Clinical manifestations
Evaluation and treatment
Inhalation disorders
Exposure to toxic gases
Pneumoconiosis

Infections of the pulmonary system
Pneumonia
Pathophysiology
Clinical manifestations
Evaluation and treatment
Tuberculosis
Pathophysiology
Clinical manifestations
Evaluation and treatment
Acute bronchitis
Influenza
Pathophysiology
Clinical manifestations
Evaluation and treatment

Lung cancer
Types of lung cancer
Non-small cell carcinoma
Small cell carcinoma
Pathophysiology
Clinical manifestations
Evaluation and treatment

Obstructive sleep apnoea
Pathophysiology
Clinical manifestations
Evaluation and treatment
Alterations of pulmonary blood flow and pressure
Pulmonary embolism
Pathophysiology
Clinical manifestations
Evaluation and treatment
Cor pulmonale
Pathophysiology
Clinical manifestations
Evaluation and treatment

Clinical manifestations of pulmonary alterations
Conditions caused by pulmonary alterations
Pulmonary oedema
Hypoxaemia
Hypercapnia
Acute respiratory failure
Atelectasis
Pneumothorax
Pleural effusion
Empyema
Aspiration
Signs and symptoms of pulmonary alterations
Dyspnoea
Cough
Hypoventilation and hyperventilation
Abnormal breathing patterns
Haemoptysis
Cyanosis

Review questions

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