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Internal Medicine Journal 43 (2013)

C L I N I C A L P E R S P E CT I V E S

Advances in chronic obstructive pulmonary disease

C. F. McDonald and Y. Khor
Respiratory and Sleep Medicine, Austin Hospital, Melbourne, Victoria, Australia

Key words Abstract

COPD, chronic obstructive pulmonary disease,
chronic, lung disease, update.
Correspondence
Christine F. McDonald, Respiratory and Sleep
Medicine, Austin Hospital, Studley Road,
Heidelberg, Vic. 3084, Australia.
Email: christine.mcdonald@austin.org.au
Received 13 November 2012; accepted 28 May
2013.
doi:10.1111/imj.12219
Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow
limitation in the presence of identifiable risk factors. Inflammation is the central patho-
logical feature in the pathogenesis of COPD. In addition to its pulmonary effects, COPD
is associated with significant extrapulmonary manifestations, including ischaemic heart
disease, osteoporosis, stroke and diabetes. Anxiety and depression are also common.
Spirometry remains the gold standard diagnostic tool. Pharmacologic and non-
pharmacologic therapy can improve symptoms, quality of life and exercise capacity and,
through their effects on reducing exacerbations, have the potential to modify disease
progression. Bronchodilators are the mainstay of pharmacotherapy, with guidelines
recommending a stepwise escalating approach. Smoking cessation is paramount in
managing COPD, with promotion of physical activity and pulmonary rehabilitation
being other key factors in management. Comorbidities should be actively sought and
managed in their own right. Given the chronicity and progressive nature of COPD,
ongoing monitoring and support with timely discussion of advanced-care planning and
end-of-life issues are recommended.

Background and epidemiology
Chronic obstructive pulmonary disease (COPD) repre-
sents a spectrum of lung diseases characterised by persis-
tent airflow limitation due to varying combinations of
small-airways disease (obstructive bronchiolitis) and
emphysema. It is a major cause of morbidity and disabil-
ity, having a prevalence of around 10% in those aged
over 40 years.1,2 By 2030 COPD is predicted to have
become the third-leading cause of death worldwide, with
90% of those deaths occurring in low- and middle-
income countries. In Australia, COPD is responsible for
4% of all deaths in recent years and is the only major
condition for which the burden of disease continues to
increase as our population ages.3 Australian death rates
from COPD per head of male population have declined
substantially since their peak in the 1970s, reflecting
changes in tobacco consumption. By contrast, female
death rates peaked in the 1990s and have stabilised,
reflecting the increased uptake of smoking by women
over the last 34 decades.3
Cigarette smoking is the most important risk factor for
COPD. Although traditional teaching suggested 1015%
of smokers develop COPD, recent studies indicate some
degree of airflow limitation is present in up to 50% of
smokers, with clinically significant COPD being present in
around 25%.4 It is increasingly recognised that a signifi-
cant proportion of patients with COPD are non-smokers.5
This proportion is generally higher in developing coun-
tries where exposure to biomass smoke for heating and
cooking is common (for example up to nearly 70% of
people in India with COPD are non-smokers),5 but is still
significant in the developed world, with just under 40% of
people in a recent New Zealand study being never-
smokers,6 and overall international figures ranging from
25% to 45%.7 Other risk factors include maternal
smoking, long-standing asthma and respiratory symp-
toms, exposure to second-hand smoke and occupational
exposures to dusts and fumes. Genetic susceptibility is an
important factor in disease development, with the most
well-established genetic factor, 1-antitrypsin deficiency,
being present in 12% of individuals with COPD.

Funding: None.
Conflict of interest: Christine McDonald has served on advisory
boards for GlaxoSmithKline, Novartis, Pfizer; received confer-
ence support from Nycomed; has given presentations at educa-
tional meetings sponsored by Boehringer Ingelheim and
Novartis.
Diagnosis
Spirometry is required to make a diagnosis of COPD. A
medical history and clinical examination may suggest the
diagnosis, but they are not reliable predictors of airflow
obstruction. In the presence of symptoms such as

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854 Internal Medicine Journal 2013 Royal Australasian College of Physicians

shortness of breath, cough and/or sputum production
and a history of relevant exposure(s), an individual with
a post-bronchodilator forced expiratory volume in one
second (FEV1) to forced vital capacity (FVC) ratio (FEV1/
FVC) of less than 0.7 (indicating airflow limitation that is
not fully reversible) is deemed to have COPD. This defi-
nition is widely accepted because of its practicality, al-
though its use may lead to overdiagnosis in the elderly (as
FEV1 declines more rapidly with age than does FVC) and
underdiagnosis in younger adults. Consequently, some
authors recommend that a lower limit of normal (fifth
percentile of the normal distribution range of FEV1/FVC
values) be applied. Unfortunately, by whatever definition
airflow obstruction is measured, spirometry continues to
be infrequently performed, even among those hospital-
ised for exacerbation of COPD in Australia. Only 51% of
a recently audited group of patients admitted to hospital
with this diagnosis had undergone lung function testing
in the 5 years prior to admission or during hospitalisa-
tion.8 This lack of confirmatory testing contributes to
both under- and overtreatment of such patients.
Pathology
COPD is a chronic inflammatory airway disease, but
differs significantly from asthma in that the inflammation
is relatively resistant to treatment with corticosteroids.
Exposure to noxious injury triggers a predominantly
neutrophilic infiltration with activation of the innate
immune response. An inflammatory cascade ensues,
with induction of type 1 and type 17 T helper cells and
the subsequent development of transforming growth
factor -induced small-airway fibrosis and matrix
metalloproteinase elastic tissue destruction.9 These
responses appear to perpetuate even after removal of the
initial stimulus10 and may be associated with spillover of
the inflammatory response from the lungs to the systemic
circulation, leading to potential downstream effects, such
as arterial stiffness and its consequences. Parenchymal
destruction is associated with loss of lung tissue elasticity
and small-airways collapse during exhalation, leading to
so-called gas trapping, while goblet cell metaplasia and
impaired mucociliary function contribute to excess
mucus accumulation and worsening obstruction.
Overlap of COPD and asthma
The definition of COPD is quite broad and may include a
variety of patients with distinct clinical and other features
who may both present differently and respond differently
to treatment (so-called clinical phenotypes). Many
patients with COPD will report a history of asthma. This
dual diagnosis or overlap syndrome may be recognised
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through symptoms associated with variable airflow
obstruction as well as incomplete reversibility of airflow
obstruction on lung function testing.11 There is increasing
evidence that patients with COPD and asthma experience
more rapid disease progression than those with either
disease alone. Airway hyperresponsiveness and an asthma
diagnosis have been associated with a greater decline in
FEV1 in both smokers and non-smokers. Patients with
overlap syndrome have worse health-related quality of
life and experience more frequent and severe respiratory
exacerbations, despite younger age and reduced lifetime
smoking exposure, when compared with those with
COPD alone.12 The evidence base for management of this
subgroup of patients is relatively limited, as they are
commonly excluded from clinical trials.
Systemic effects and comorbidities
It has been proposed that the term chronic systemic
inflammatory syndrome be applied to COPD in order to
highlight the underlying inflammatory response
common to both COPD and many of its associated
comorbidities, which are also commonly associated with
smoking.13 Features include systemic oxidative stress,
changes in vasomotor and endothelial function and
enhanced circulating concentrations of procoagulant
factors.13 Using a UK-wide validated primary care data-
base, Feary et al. observed a fivefold increase in risk of
cardiovascular disease, a threefold increase in risk of
stroke and a twofold increase in risk of diabetes in
patients with physician-diagnosed COPD.14 Suggested
mechanisms, over and above smoking, that may be
implicated in these interactions include increased aortic
stiffness and associated left ventricular dysfunction, as
well as increased platelet activation.15 Of note is the fact
that having COPD increases the risk of lung cancer by up
to 4.5-fold among long-term smokers.16 Considering
lung- and non-lung-related manifestations of COPD as a
syndrome akin to the way in which we think of the
metabolic syndrome, for example, may encourage inves-
tigation and appropriate management of some of the
more common comorbidities described in association
with COPD, including those mentioned as well as osteo-
porosis, hyperlipidaemia, hypertension, skeletal muscle
abnormalities, anxiety and depression.
Acute exacerbations of COPD
An exacerbation of COPD is defined as an acute event
characterised by a worsening of the patients respiratory
symptoms that is beyond normal day-to-day variations
and necessitates a change in medication.17 COPD exacer-
bations are associated with considerable morbidity,
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mortality and healthcare costs. They are the second
leading cause of hospitalisations in Australia.18 Exacerba-
tions become more frequent as the severity of COPD
worsens.19 Following hospitalisation for an exacerbation,
quality of life and lung function decline, and patients are at
risk for further serious exacerbations. A primary goal of
treatment in COPD is therefore to reduce exacerbations.
Triggers for acute exacerbations include viral and bacterial
infections as well as environmental pollutants, heart
failure, pulmonary embolism and other factors.20 Prompt
treatment with short-acting bronchodilators, antibiotics as
appropriate and corticosteroids has been demonstrated to
hasten resolution and reduce need for hospitalisation.21
Non-invasive ventilatory support is indicated for hype-
rcapnic respiratory failure and is effective in avoiding
intubation and reducing risk of death.22 Mortality after
hospitalisation for acute exacerbation may be as high as
22% at 12 months,23 although more recent data suggest a
trend towards improved outcomes.24 An admission to
hospital with an exacerbation of COPD is a sentinel event
that should give pause for review of current management,
including preventive therapies. Such episodes should act
as a trigger for discussion about advanced-care planning
and wishes concerning non-invasive and invasive venti-
lation should the need arise. Recent data suggest early
pulmonary rehabilitation following exacerbation and
hospitalisation may decrease readmission, and National
Institute for Health and Care Excellence guidelines
recommend this as standard of care.25
Management of stable COPD
Although severity of airflow obstruction is classified
according to FEV1 (as a percentage of the predicted
normal value), and spirometry is essential in determining
whether the probable cause of respiratory symptoms is
COPD, clinical criteria, such as degree of breathlessness
induced by daily activities and frequency of exacerba-
tions, should also be used when evaluating overall
disease severity.26,27 Validated tools, such as the modified
Medical Research Council breathlessness scale and the
COPD Assessment Test, may be helpful in assessing
disease impact and treatment response.17
The goals of management in stable COPD are to reduce
symptoms, reduce the frequency and severity of exacer-
bations, improve exercise tolerance and health-related
quality of life, slow disease progression and reduce
mortality. Both pharmacologic and non-pharmacologic
strategies may be employed. Guidelines for COPD man-
agement recommend a stepwise escalation of therapy
based on disease severity. Two guidelines commonly used
in Australia are the Global Initiative for Chronic Obstruc-
tive Lung Disease (GOLD) Strategy Document17 and the
856
locally developed COPD-X guideline.26 The recently
updated (2011) GOLD Document has adopted a new
stratification for disease severity, based on exacerbation
rates and symptom scores in addition to degree of airflow
obstruction. This is not significantly different from
COPD-X, which determines severity based on clinical
history and functional assessment as well as spirometry
and emphasises consideration of the presence and treat-
ment of complications and comorbidities in their own
right.
Smoking cessation
Preventing or limiting lung damage through smoking
cessation should be the foremost goal for all physicians
managing COPD. Of course, all smokers should be
encouraged to stop smoking, whether or not they have
COPD. Smoking cessation reduces rate of decline of FEV1
as well as improving respiratory symptoms and health-
related quality of life. To date, smoking cessation and
home oxygen therapy (in severely hypoxaemic individ-
uals) are the only strategies conclusively demonstrated to
improve mortality in COPD. Even brief counselling can
be effective. But additional strategies may be required for
patients who continue to smoke despite having lung
disease. All forms of nicotine replacement therapy (NRT)
appear to assist smoking cessation in dependent smokers,
and NRT is safe even in acute coronary syndromes.
Agents such as the antidepressant and selective
catecholamine reuptake inhibitor buproprion and the
42 nicotinic acetylcholine receptor partial agonist
varenicline are also effective. All pharmacologic therapies
must be combined with support and counselling for
maximum efficacy.26
Pharmacotherapy
The aims of pharmacotherapy in COPD are to relieve
symptoms (notably, breathlessness) and to prevent
deterioration, either by reducing exacerbations or by
reducing decline in quality of life, or both.
Bronchodilators remain the mainstay of therapy for
COPD and include short- and long-acting 2 agonists
(SABA and LABA) as well as short- and long-acting
muscarinic antagonists (SAMA and LAMA).They can
impact the gas trapping that is a feature of COPD, induc-
ing improvements in inspiratory capacity and end-
expiratory lung volume that may improve breathlessness
and exercise capacity even in the absence of a demon-
strable bronchodilator response on simple spirometric
testing. In addition to improving symptom control, both
LAMA and LABA have been shown to reduce exacerba-
tions and hospitalisations and to improve lung function.27
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Despite the relative corticosteroid insensitivity of the
inflammatory response in COPD, the addition of an
inhaled corticosteroid is recommended in patients with
moderate to severe COPD, especially in those with recur-
rent exacerbations, because of additional benefits in
terms of reduced exacerbations as well as improved
quality of life. These small additional benefits must be
balanced against an increased risk for pneumonia and
local side-effects of dysphonia and upper-airway candidi-
asis.28 Inhaler technique must be assessed regularly, and
medications reviewed and either continued or discon-
tinued based upon treatment response and tolerability. It
is important that both patient and treating doctor are
clear as to the expectations from treatment (for example,
whether the treatment aims purely at symptom control
or is aimed at longer-term outcomes such as prevention
of exacerbations and/or hospitalisations, or both).
Newer therapies
Indacaterol is a novel ultra-LABA with 24-h bronchodi-
lator efficacy allowing once-daily dosing. It may be
superior to conventional LABA in patients with moderate
to severe COPD and is comparable in efficacy with
tiotropium.29 The combination of indacaterol plus
tiotropium provides additional bronchodilation com-
pared with each treatment alone.30 As understanding
of COPD inflammatory pathways increases, newer
therapies targeting inflammatory molecules have been
developed. Roflumilast, a selective phosphodiesterase-4
inhibitor, has recently been approved for use in several
countries for treatment of severe COPD (although not yet
in Australia). It has been shown to be effective, with
well-tolerated side effects,31 and may be suited for
patients with severe COPD and frequent exacerbations.32
However, long-term data on efficacy and adverse events
are not yet available, and its role in patients already
receiving standard combination therapy is yet to be deter-
mined.33 Although standard-dose theophylline is consid-
ered a third- or fourth-line treatment in COPD, low-dose
theophylline has recently been raised as a possible
adjunct to current inhaled therapies, given experimental
data demonstrating it enhances anti-inflammatory effects
of inhaled corticosteroids in COPD airways through
modification of histone deacetylase-2. Nonetheless,
large-scale clinical trials investigating exacerbation
reduction through this mechanism are awaited.34 Given
the known anti-inflammatory and immunomodulatory
effects of macrolide antibiotics, several studies have
evaluated their effects on reducing COPD exacerbations.
A recent study found a decreased rate of exacerbations in
patients treated with daily azithromcyin.35 Adverse
effects included ototoxicity and increased macrolide
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Advances in COPD
resistance. Azithromycin is also associated with cardiac
toxicity.36 It remains to be seen what the treatment effect
of chronic macrolide therapy is in COPD patients treated
maximally with conventional therapies and whether
benefits will outweigh risks to the individual and the
community from their more widespread use.
Management of cardiac disease as
a comorbidity
The importance of managing the common comorbidities
in COPD, which may be considered either as fellow
travellers or as components of a chronic systemic
inflammatory complex, is increasingly recognised. Many
patients with COPD die from cardiovascular disease,
and the prevalence of ventricular dysfunction in
patients with COPD ranges from 9% to 52%. Diagnos-
ing cardiac disease in COPD is made more difficult by
similar presenting features, which, in both cases, may
include breathlessness, fatigue and even chest discom-
fort. Beta-blockers have proven mortality benefits in
cardiac disease, but their use remains low in patients
with COPD because of their potential to provoke acute
bronchospasm and worsen respiratory symptoms. Con-
cerns have been allayed to some extent by a recent
meta-analysis suggesting that cardioselective beta-
blockers are safe and well tolerated even in patients
with severe airflow obstruction.37 Nonetheless, the
included studies were of short duration in small
numbers of patients, thus providing little guidance
about long-term safety and potential morbidity. Recent
large observational database studies of patients with
COPD added reassurance with the finding of beneficial
effects of beta-blockers on overall mortality, without
adverse effects on lung function.38,39 European Society
of Cardiology guidelines assert that COPD is not a con-
traindication to the use of beta-blockers.40 Although
low-dose initiation and gradual up-titration is recom-
mended, and mild deterioration in pulmonary function
and symptoms should not necessarily prompt discon-
tinuation, prudence would dictate a cautious approach
in the absence of long-term prospective data.
Other comorbidities should be managed according to
appropriate guidelines.
Vaccination
Influenza vaccine reduces the number of acute exacer-
bations that occur in persons with COPD, but evidence
regarding its effects on hospitalisations and mortality is
inconclusive. Pneumococcal vaccine reduces the inci-
dence of invasive pneumococcal disease, but there is a
lack of evidence concerning its effect on morbidity or
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McDonald & Khor
mortality in people with COPD.41 National Health and
Medical Research Council guidelines recommend yearly
influenza vaccinations and up-to-date pneumococcal
vaccination for people with COPD.
Activity promotion, pulmonary
rehabilitation and disease management
When patients with COPD begin to feel short of breath
with activity, they typically reduce their activities and
become more sedentary. COPD results in systemic func-
tional limitations that lead to physical deconditioning and
the development of the so-called dyspnoea spiral: pro-
gressive deconditioning and ever-worsening dyspnoea.
Regular physical activity is recommended for all people
with COPD and has been associated with reduced risk of
hospital admissions.
In people with moderate to severe COPD, participation
in outpatient pulmonary rehabilitation (generally around
68 weeks of graded exercises and education incorporat-
ing self-management education, provided by a multidis-
ciplinary team) is associated with improved exercise
capacity, less breathlessness and better quality of life and,
in those who have been hospitalised, with reduced hos-
pital admissions and mortality.42
Action plans have been effective in asthma. They
allow patients to develop coping skills, to anticipate
early exacerbation symptoms, to self-initiate appropriate
treatment and to seek medical advice prior to significant
deterioration. COPD exacerbations are common in
patients with moderate to severe COPD and may lead to
hospitalisation. Trials assessing the effects of action plans
in COPD management have shown conflicting results,
with variable adjuncts to patient care in these trials
likely contributors. Those with positive results, such as
expedited exacerbation recovery and reduced hospital
admissions, have included additional supports, such as
intensive education and case management.4345 In con-
trast, action plans with limited or no self-management
education and no case management have little benefi-
cial effect.46 In view of the healthcare cost implications
of COPD exacerbations, various models of self-
management have been initiated in national healthcare
systems, but the evidence for benefit has not been
confirmed. Programmes may include self-management
education about disease, optimisation of evidence-based
medications, information and support from case man-
agers and institution of self-management principles. A
2007 Cochrane meta-analysis concluded that self-
management education in COPD was likely associated
with reduced hospital admissions and no detrimental
effects, but determined that larger randomised con-
trolled trials were required before clear recommenda-
858
tions could be made.47 A recent UK study included a
high-risk group of patients with COPD who had been
recently hospitalised and reported no overall effect of a
self-management programme on readmissions and
death.48 However, only 42% of the patients were suc-
cessful self-managers, and these individuals did have
improved outcomes. A recent US study has raised
concern.49 This multicentre trial of a comprehensive
COPD care programme was discontinued prematurely
by the data monitoring committee after only 44% of
the planned 960 patients were enrolled, because of an
excess of deaths in the intervention group (28 vs 10).
The primary outcome of admission did not differ
between the groups. It is not clear why so many deaths
occurred in the intervention group. Although perhaps
this was a chance occurrence, more studies are needed
to determine the role of disease management in COPD.
Oxygen therapy
The use of domiciliary oxygen is common at the more
severe end of the COPD spectrum. In 2005 21 000 Aus-
tralians were receiving domiciliary oxygen therapy, at an
estimated annual cost of over A$32 million, with the
major indication being COPD.50 Long-term continuous
oxygen therapy has been proven to offer survival benefits
in patients with COPD and severe hypoxaemia (PaO2
55 mmHg or 5559 mmHg with evidence of end-organ
damage). However, the role of oxygen therapy in patients
with exertional desaturation, nocturnal hypoxaemia or
resting mild to moderate hypoxaemia is less clear. Recent
studies suggest an absence of long-term effects on breath-
lessness or quality of life from the use of ambulatory
oxygen therapy in normoxaemic or mildly hypoxaemic
patients with COPD who desaturate with exertion, even
though they may demonstrate small acute benefits
during laboratory-based exercise tests.51,52 Nonetheless,
occasional so-called n-of-1 trials may be of use in some
individuals.52 Isolated nocturnal hypoxaemia is not
uncommon in COPD patients, particularly during rapid
eye movement sleep. However, it has not been shown to
lead to worse quality of life, daytime hypoxaemia or
pulmonary hypertension. Limited studies have not con-
sistently shown beneficial effects in sleep quality, pulmo-
nary haemodynamics or survival over 2 years with
nocturnal supplemental oxygen.5355 Similarly, patients
with COPD and resting mild-to-moderate hypoxaemia
have not shown a survival benefit with domiciliary
oxygen therapy. The currently recruiting US Long-term
Oxygen Treatment Trial (NCT00692198) may provide
more data regarding the effects of domiciliary oxygen in
the latter patient subgroup.
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Non-invasive ventilation:
acute versus stable
Non-invasive ventilation (NIV) is considered the standard
of care for patients with acute exacerbations of COPD
associated with hypercapnic respiratory failure and aci-
dosis. It has been shown to reduce mortality, need for
intubation, treatment failure, treatment complications
and length of hospital stay.22 Patients who survive after
an episode of acute hypercapnic respiratory failure
treated with NIV are at high risk of readmission and
life-threatening events during the following year.
Although there are theoretical reasons why chronic NIV
may benefit such patients, results from randomised con-
trolled trials have been conflicting. A systematic review
concluded there was no consistent clinically or statisti-
cally significant effect of domiciliary NIV on lung func-
tion, gas exchange, exercise tolerance, respiratory muscle
strength or sleep efficiency.56 However, many included
studies had small sample sizes, included patients without
significant hypercapnia, were of limited duration and/or
used low levels of inspiratory pressure support. An Aus-
tralian study randomised 144 patients to receive home
NIV plus long-term home oxygen therapy versus oxygen
alone.57 Home NIV was associated with an improvement
in survival up to 3.5 years, at the expense of worse
quality of life. In summary, NIV may be a therapeutic
option in stable COPD patients with chronic ventilatory
failure, but further long-term randomised controlled
trials are awaited.
Interventional therapy: surgery
and devices
In patients with very severe COPD who remain incapaci-
tated by dyspnoea despite maximal therapy, various sur-
gical approaches have been trialled. Currently available
surgical interventions include lung transplantation, lung
volume reduction surgery and bullectomy. Since the first
successful clinical lung transplant in 1983, transplanta-
tion has become a treatment option for selected patients
with end-stage COPD, with improved survival. However,
transplantation is limited by donor availability, the need
for lifelong immunosuppression and its complications
and the development of chronic allograft dysfunction in
the form of bronchiolitis obliterans. In patients with
emphysema, lung volume reduction surgery (LVRS) is
aimed at relieving the hyperinflation and gas trapping
associated with inadequate lung emptying and its associ-
ated mechanical disadvantage. LVRS and bullectomy in
selected patients have been shown to improve lung func-
tion and exercise capacity in the long term, although
perioperative morbidity (most commonly parenchymal
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air leaks) and mortality are significant.58 The majority of
patients with end-stage COPD are not suitable surgical
candidates because of their physiological fragility.
Current selection guidelines for LVRS are largely based
upon the results of the National Emphysema Treatment
Trial inclusion criteria and outcome data and include
bilateral, upper-lobe-predominant emphysema with sig-
nificant hyperinflation and air trapping and a low
maximal workload after pulmonary rehabilitation.59
In order to obviate the need for surgery, there has been
considerable recent interest in the development of
bronchoscopic techniques for lung volume reduction.
Modalities employed have included endobronchial valves
or blockers, airway bypass, biologic sealants and airway
implants. Endobronchial one-way valves block the
airway leading to the targeted emphysematous lung.
Apart from allowing air to be vented and preventing
refilling, these valves also allow expulsion of mucus to
minimise postobstructive infection. Modest improve-
ments in lung function, exercise tolerance and symptoms
have been demonstrated in selected patients with
advanced heterogenous emphysema using endo-
bronchial valves, although efficacy is variable and
adverse effects include increased risk of COPD exacerba-
tions, haemoptysis and pneumonia.60 Bronchoscopic
thermal vapour ablation (BTVA) is a newer technique
that utilises heated water vapour to induce thermal reac-
tion and subsequent inflammatory response with perma-
nent fibrosis and atelectasis, leading to reduction in
volume of the targeted regions. Australia was involved in
the first human study of BTVA for lung volume reduction
in upper-lobe-predominant emphysema. Results indicate
that BTVA significantly improves lung function, symp-
toms and exercise tolerance.61 The most common adverse
effects of BTVA are lower respiratory events, pneumonia
and haemoptysis. These complex procedures require
careful patient selection and assessment by a multidi-
sciplinary team at a specialised centre to ensure best
outcomes.
Prognosis, palliative care and
advanced-care planning
Lung function impairment is a strong predictor of mor-
tality; however, use of lung function alone to classify
disease severity does not capture the multidimensional
nature of COPD. In patients with established COPD a
variety of indices has been proposed that enhance the
ability to predict mortality. Degree of hyperinflation as
measured by inspiratory capacity/total lung capacity ratio
is more closely associated with all cause and COPD mor-
tality than FEV1.62 The BODE index, incorporating body
mass index, degree of obstruction as measured by FEV1,
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dyspnoea score and exercise capacity as measured by 6
minutes walk distance into a common index, enhances
the ability to predict mortality.63 Further, the presence of
comorbid disease increases the risk of both hospitalisation
and mortality. The predominant causes of mortality in
patients with mild disease are cardiac disease and malig-
nancy, while as COPD severity increases, deaths due to
respiratory disease are increasingly common.
Severe dyspnoea, cough, fatigue, social isolation,
anxiety and depression are all features of late-stage COPD
that adversely impact quality of life. The COPD disease
course is often punctuated by recurrent exacerbations
that may require hospitalisation and consideration of
assisted ventilation. Hospitalisation for acute exacerba-
tion increases subsequent mortality risk. As the disease
progresses a more palliative approach to care may be
appropriate. Determining prognosis in end-stage COPD is
difficult; however, characteristics that should trigger dis-
cussions about a palliative approach to care, advanced-
care planning and end-of-life issues include FEV1 < 25%,
oxygen dependence, respiratory failure, heart failure or
other comorbidities, weight loss or cachexia, decreased
functional status, increasing dependence on others, and
advancing age.64 Ideally, end-of-life discussions, includ-
ing resuscitation and intubation wishes, and advanced-
care planning, including consideration of the conferment
of a medical enduring power of attorney, should occur in
an outpatient setting when the patients condition is
relatively stable.
Conclusion
COPD is a common disease associated with significant
morbidity and mortality. Spirometry is key to its diagnosis
and is required in order to avoid under- and
overtreatment. Smoking cessation and oxygen therapy in
those who are hypoxaemic may reduce mortality.
Pharmacologic and non-pharmacologic therapy can
improve symptoms, quality of life and exercise capacity
and, through their effects on reducing exacerbations,
have the potential to modify disease progression.
Comorbidities are common and require targeted
treatment.

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