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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. Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow
limitation in the presence of identifiable risk factors. Inflammation is the central patho-
Correspondence logical feature in the pathogenesis of COPD. In addition to its pulmonary effects, COPD
Christine F. McDonald, Respiratory and Sleep is associated with significant extrapulmonary manifestations, including ischaemic heart
Medicine, Austin Hospital, Studley Road, disease, osteoporosis, stroke and diabetes. Anxiety and depression are also common.
Heidelberg, Vic. 3084, Australia. Spirometry remains the gold standard diagnostic tool. Pharmacologic and non-
Email: christine.mcdonald@austin.org.au pharmacologic therapy can improve symptoms, quality of life and exercise capacity and,
through their effects on reducing exacerbations, have the potential to modify disease
Received 13 November 2012; accepted 28 May progression. Bronchodilators are the mainstay of pharmacotherapy, with guidelines
2013. recommending a stepwise escalating approach. Smoking cessation is paramount in
managing COPD, with promotion of physical activity and pulmonary rehabilitation
doi:10.1111/imj.12219 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 Cigarette smoking is the most important risk factor for
COPD. Although traditional teaching suggested 1015%
Chronic obstructive pulmonary disease (COPD) repre- of smokers develop COPD, recent studies indicate some
sents a spectrum of lung diseases characterised by persis- degree of airflow limitation is present in up to 50% of
tent airflow limitation due to varying combinations of smokers, with clinically significant COPD being present in
small-airways disease (obstructive bronchiolitis) and around 25%.4 It is increasingly recognised that a signifi-
emphysema. It is a major cause of morbidity and disabil- cant proportion of patients with COPD are non-smokers.5
ity, having a prevalence of around 10% in those aged This proportion is generally higher in developing coun-
over 40 years.1,2 By 2030 COPD is predicted to have tries where exposure to biomass smoke for heating and
become the third-leading cause of death worldwide, with cooking is common (for example up to nearly 70% of
90% of those deaths occurring in low- and middle- people in India with COPD are non-smokers),5 but is still
income countries. In Australia, COPD is responsible for significant in the developed world, with just under 40% of
4% of all deaths in recent years and is the only major people in a recent New Zealand study being never-
condition for which the burden of disease continues to smokers,6 and overall international figures ranging from
increase as our population ages.3 Australian death rates 25% to 45%.7 Other risk factors include maternal
from COPD per head of male population have declined smoking, long-standing asthma and respiratory symp-
substantially since their peak in the 1970s, reflecting toms, exposure to second-hand smoke and occupational
changes in tobacco consumption. By contrast, female exposures to dusts and fumes. Genetic susceptibility is an
death rates peaked in the 1990s and have stabilised, important factor in disease development, with the most
reflecting the increased uptake of smoking by women well-established genetic factor, 1-antitrypsin deficiency,
over the last 34 decades.3 being present in 12% of individuals with COPD.

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

2013 The Authors


854 Internal Medicine Journal 2013 Royal Australasian College of Physicians
Advances in COPD

shortness of breath, cough and/or sputum production through symptoms associated with variable airflow
and a history of relevant exposure(s), an individual with obstruction as well as incomplete reversibility of airflow
a post-bronchodilator forced expiratory volume in one obstruction on lung function testing.11 There is increasing
second (FEV1) to forced vital capacity (FVC) ratio (FEV1/ evidence that patients with COPD and asthma experience
FVC) of less than 0.7 (indicating airflow limitation that is more rapid disease progression than those with either
not fully reversible) is deemed to have COPD. This defi- disease alone. Airway hyperresponsiveness and an asthma
nition is widely accepted because of its practicality, al- diagnosis have been associated with a greater decline in
though its use may lead to overdiagnosis in the elderly (as FEV1 in both smokers and non-smokers. Patients with
FEV1 declines more rapidly with age than does FVC) and overlap syndrome have worse health-related quality of
underdiagnosis in younger adults. Consequently, some life and experience more frequent and severe respiratory
authors recommend that a lower limit of normal (fifth exacerbations, despite younger age and reduced lifetime
percentile of the normal distribution range of FEV1/FVC smoking exposure, when compared with those with
values) be applied. Unfortunately, by whatever definition COPD alone.12 The evidence base for management of this
airflow obstruction is measured, spirometry continues to subgroup of patients is relatively limited, as they are
be infrequently performed, even among those hospital- commonly excluded from clinical trials.
ised for exacerbation of COPD in Australia. Only 51% of
a recently audited group of patients admitted to hospital
Systemic effects and comorbidities
with this diagnosis had undergone lung function testing
in the 5 years prior to admission or during hospitalisa- It has been proposed that the term chronic systemic
tion.8 This lack of confirmatory testing contributes to inflammatory syndrome be applied to COPD in order to
both under- and overtreatment of such patients. highlight the underlying inflammatory response
common to both COPD and many of its associated
comorbidities, which are also commonly associated with
Pathology
smoking.13 Features include systemic oxidative stress,
COPD is a chronic inflammatory airway disease, but changes in vasomotor and endothelial function and
differs significantly from asthma in that the inflammation enhanced circulating concentrations of procoagulant
is relatively resistant to treatment with corticosteroids. factors.13 Using a UK-wide validated primary care data-
Exposure to noxious injury triggers a predominantly base, Feary et al. observed a fivefold increase in risk of
neutrophilic infiltration with activation of the innate cardiovascular disease, a threefold increase in risk of
immune response. An inflammatory cascade ensues, stroke and a twofold increase in risk of diabetes in
with induction of type 1 and type 17 T helper cells and patients with physician-diagnosed COPD.14 Suggested
the subsequent development of transforming growth mechanisms, over and above smoking, that may be
factor -induced small-airway fibrosis and matrix implicated in these interactions include increased aortic
metalloproteinase elastic tissue destruction.9 These stiffness and associated left ventricular dysfunction, as
responses appear to perpetuate even after removal of the well as increased platelet activation.15 Of note is the fact
initial stimulus10 and may be associated with spillover of that having COPD increases the risk of lung cancer by up
the inflammatory response from the lungs to the systemic to 4.5-fold among long-term smokers.16 Considering
circulation, leading to potential downstream effects, such lung- and non-lung-related manifestations of COPD as a
as arterial stiffness and its consequences. Parenchymal syndrome akin to the way in which we think of the
destruction is associated with loss of lung tissue elasticity metabolic syndrome, for example, may encourage inves-
and small-airways collapse during exhalation, leading to tigation and appropriate management of some of the
so-called gas trapping, while goblet cell metaplasia and more common comorbidities described in association
impaired mucociliary function contribute to excess with COPD, including those mentioned as well as osteo-
mucus accumulation and worsening obstruction. porosis, hyperlipidaemia, hypertension, skeletal muscle
abnormalities, anxiety and depression.

Overlap of COPD and asthma


Acute exacerbations of COPD
The definition of COPD is quite broad and may include a
variety of patients with distinct clinical and other features An exacerbation of COPD is defined as an acute event
who may both present differently and respond differently characterised by a worsening of the patients respiratory
to treatment (so-called clinical phenotypes). Many symptoms that is beyond normal day-to-day variations
patients with COPD will report a history of asthma. This and necessitates a change in medication.17 COPD exacer-
dual diagnosis or overlap syndrome may be recognised bations are associated with considerable morbidity,

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Internal Medicine Journal 2013 Royal Australasian College of Physicians 855
McDonald & Khor

mortality and healthcare costs. They are the second locally developed COPD-X guideline.26 The recently
leading cause of hospitalisations in Australia.18 Exacerba- updated (2011) GOLD Document has adopted a new
tions become more frequent as the severity of COPD stratification for disease severity, based on exacerbation
worsens.19 Following hospitalisation for an exacerbation, rates and symptom scores in addition to degree of airflow
quality of life and lung function decline, and patients are at obstruction. This is not significantly different from
risk for further serious exacerbations. A primary goal of COPD-X, which determines severity based on clinical
treatment in COPD is therefore to reduce exacerbations. history and functional assessment as well as spirometry
Triggers for acute exacerbations include viral and bacterial and emphasises consideration of the presence and treat-
infections as well as environmental pollutants, heart ment of complications and comorbidities in their own
failure, pulmonary embolism and other factors.20 Prompt right.
treatment with short-acting bronchodilators, antibiotics as
appropriate and corticosteroids has been demonstrated to
Smoking cessation
hasten resolution and reduce need for hospitalisation.21
Non-invasive ventilatory support is indicated for hype- Preventing or limiting lung damage through smoking
rcapnic respiratory failure and is effective in avoiding cessation should be the foremost goal for all physicians
intubation and reducing risk of death.22 Mortality after managing COPD. Of course, all smokers should be
hospitalisation for acute exacerbation may be as high as encouraged to stop smoking, whether or not they have
22% at 12 months,23 although more recent data suggest a COPD. Smoking cessation reduces rate of decline of FEV1
trend towards improved outcomes.24 An admission to as well as improving respiratory symptoms and health-
hospital with an exacerbation of COPD is a sentinel event related quality of life. To date, smoking cessation and
that should give pause for review of current management, home oxygen therapy (in severely hypoxaemic individ-
including preventive therapies. Such episodes should act uals) are the only strategies conclusively demonstrated to
as a trigger for discussion about advanced-care planning improve mortality in COPD. Even brief counselling can
and wishes concerning non-invasive and invasive venti- be effective. But additional strategies may be required for
lation should the need arise. Recent data suggest early patients who continue to smoke despite having lung
pulmonary rehabilitation following exacerbation and disease. All forms of nicotine replacement therapy (NRT)
hospitalisation may decrease readmission, and National appear to assist smoking cessation in dependent smokers,
Institute for Health and Care Excellence guidelines and NRT is safe even in acute coronary syndromes.
recommend this as standard of care.25 Agents such as the antidepressant and selective
catecholamine reuptake inhibitor buproprion and the
42 nicotinic acetylcholine receptor partial agonist
Management of stable COPD
varenicline are also effective. All pharmacologic therapies
Although severity of airflow obstruction is classified must be combined with support and counselling for
according to FEV1 (as a percentage of the predicted maximum efficacy.26
normal value), and spirometry is essential in determining
whether the probable cause of respiratory symptoms is
Pharmacotherapy
COPD, clinical criteria, such as degree of breathlessness
induced by daily activities and frequency of exacerba- The aims of pharmacotherapy in COPD are to relieve
tions, should also be used when evaluating overall symptoms (notably, breathlessness) and to prevent
disease severity.26,27 Validated tools, such as the modified deterioration, either by reducing exacerbations or by
Medical Research Council breathlessness scale and the reducing decline in quality of life, or both.
COPD Assessment Test, may be helpful in assessing Bronchodilators remain the mainstay of therapy for
disease impact and treatment response.17 COPD and include short- and long-acting 2 agonists
The goals of management in stable COPD are to reduce (SABA and LABA) as well as short- and long-acting
symptoms, reduce the frequency and severity of exacer- muscarinic antagonists (SAMA and LAMA).They can
bations, improve exercise tolerance and health-related impact the gas trapping that is a feature of COPD, induc-
quality of life, slow disease progression and reduce ing improvements in inspiratory capacity and end-
mortality. Both pharmacologic and non-pharmacologic expiratory lung volume that may improve breathlessness
strategies may be employed. Guidelines for COPD man- and exercise capacity even in the absence of a demon-
agement recommend a stepwise escalation of therapy strable bronchodilator response on simple spirometric
based on disease severity. Two guidelines commonly used testing. In addition to improving symptom control, both
in Australia are the Global Initiative for Chronic Obstruc- LAMA and LABA have been shown to reduce exacerba-
tive Lung Disease (GOLD) Strategy Document17 and the tions and hospitalisations and to improve lung function.27

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856 Internal Medicine Journal 2013 Royal Australasian College of Physicians
Advances in COPD

Despite the relative corticosteroid insensitivity of the resistance. Azithromycin is also associated with cardiac
inflammatory response in COPD, the addition of an toxicity.36 It remains to be seen what the treatment effect
inhaled corticosteroid is recommended in patients with of chronic macrolide therapy is in COPD patients treated
moderate to severe COPD, especially in those with recur- maximally with conventional therapies and whether
rent exacerbations, because of additional benefits in benefits will outweigh risks to the individual and the
terms of reduced exacerbations as well as improved community from their more widespread use.
quality of life. These small additional benefits must be
balanced against an increased risk for pneumonia and
Management of cardiac disease as
local side-effects of dysphonia and upper-airway candidi-
a comorbidity
asis.28 Inhaler technique must be assessed regularly, and
medications reviewed and either continued or discon- The importance of managing the common comorbidities
tinued based upon treatment response and tolerability. It in COPD, which may be considered either as fellow
is important that both patient and treating doctor are travellers or as components of a chronic systemic
clear as to the expectations from treatment (for example, inflammatory complex, is increasingly recognised. Many
whether the treatment aims purely at symptom control patients with COPD die from cardiovascular disease,
or is aimed at longer-term outcomes such as prevention and the prevalence of ventricular dysfunction in
of exacerbations and/or hospitalisations, or both). 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
Newer therapies
include breathlessness, fatigue and even chest discom-
Indacaterol is a novel ultra-LABA with 24-h bronchodi- fort. Beta-blockers have proven mortality benefits in
lator efficacy allowing once-daily dosing. It may be cardiac disease, but their use remains low in patients
superior to conventional LABA in patients with moderate with COPD because of their potential to provoke acute
to severe COPD and is comparable in efficacy with bronchospasm and worsen respiratory symptoms. Con-
tiotropium.29 The combination of indacaterol plus cerns have been allayed to some extent by a recent
tiotropium provides additional bronchodilation com- meta-analysis suggesting that cardioselective beta-
pared with each treatment alone.30 As understanding blockers are safe and well tolerated even in patients
of COPD inflammatory pathways increases, newer with severe airflow obstruction.37 Nonetheless, the
therapies targeting inflammatory molecules have been included studies were of short duration in small
developed. Roflumilast, a selective phosphodiesterase-4 numbers of patients, thus providing little guidance
inhibitor, has recently been approved for use in several about long-term safety and potential morbidity. Recent
countries for treatment of severe COPD (although not yet large observational database studies of patients with
in Australia). It has been shown to be effective, with COPD added reassurance with the finding of beneficial
well-tolerated side effects,31 and may be suited for effects of beta-blockers on overall mortality, without
patients with severe COPD and frequent exacerbations.32 adverse effects on lung function.38,39 European Society
However, long-term data on efficacy and adverse events of Cardiology guidelines assert that COPD is not a con-
are not yet available, and its role in patients already traindication to the use of beta-blockers.40 Although
receiving standard combination therapy is yet to be deter- low-dose initiation and gradual up-titration is recom-
mined.33 Although standard-dose theophylline is consid- mended, and mild deterioration in pulmonary function
ered a third- or fourth-line treatment in COPD, low-dose and symptoms should not necessarily prompt discon-
theophylline has recently been raised as a possible tinuation, prudence would dictate a cautious approach
adjunct to current inhaled therapies, given experimental in the absence of long-term prospective data.
data demonstrating it enhances anti-inflammatory effects Other comorbidities should be managed according to
of inhaled corticosteroids in COPD airways through appropriate guidelines.
modification of histone deacetylase-2. Nonetheless,
large-scale clinical trials investigating exacerbation
Vaccination
reduction through this mechanism are awaited.34 Given
the known anti-inflammatory and immunomodulatory Influenza vaccine reduces the number of acute exacer-
effects of macrolide antibiotics, several studies have bations that occur in persons with COPD, but evidence
evaluated their effects on reducing COPD exacerbations. regarding its effects on hospitalisations and mortality is
A recent study found a decreased rate of exacerbations in inconclusive. Pneumococcal vaccine reduces the inci-
patients treated with daily azithromcyin.35 Adverse dence of invasive pneumococcal disease, but there is a
effects included ototoxicity and increased macrolide lack of evidence concerning its effect on morbidity or

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Internal Medicine Journal 2013 Royal Australasian College of Physicians 857
McDonald & Khor

mortality in people with COPD.41 National Health and tions could be made.47 A recent UK study included a
Medical Research Council guidelines recommend yearly high-risk group of patients with COPD who had been
influenza vaccinations and up-to-date pneumococcal recently hospitalised and reported no overall effect of a
vaccination for people with COPD. self-management programme on readmissions and
death.48 However, only 42% of the patients were suc-
cessful self-managers, and these individuals did have
Activity promotion, pulmonary
improved outcomes. A recent US study has raised
rehabilitation and disease management
concern.49 This multicentre trial of a comprehensive
When patients with COPD begin to feel short of breath COPD care programme was discontinued prematurely
with activity, they typically reduce their activities and by the data monitoring committee after only 44% of
become more sedentary. COPD results in systemic func- the planned 960 patients were enrolled, because of an
tional limitations that lead to physical deconditioning and excess of deaths in the intervention group (28 vs 10).
the development of the so-called dyspnoea spiral: pro- The primary outcome of admission did not differ
gressive deconditioning and ever-worsening dyspnoea. between the groups. It is not clear why so many deaths
Regular physical activity is recommended for all people occurred in the intervention group. Although perhaps
with COPD and has been associated with reduced risk of this was a chance occurrence, more studies are needed
hospital admissions. to determine the role of disease management in COPD.
In people with moderate to severe COPD, participation
in outpatient pulmonary rehabilitation (generally around
68 weeks of graded exercises and education incorporat-
Oxygen therapy
ing self-management education, provided by a multidis-
ciplinary team) is associated with improved exercise The use of domiciliary oxygen is common at the more
capacity, less breathlessness and better quality of life and, severe end of the COPD spectrum. In 2005 21 000 Aus-
in those who have been hospitalised, with reduced hos- tralians were receiving domiciliary oxygen therapy, at an
pital admissions and mortality.42 estimated annual cost of over A$32 million, with the
Action plans have been effective in asthma. They major indication being COPD.50 Long-term continuous
allow patients to develop coping skills, to anticipate oxygen therapy has been proven to offer survival benefits
early exacerbation symptoms, to self-initiate appropriate in patients with COPD and severe hypoxaemia (PaO2
treatment and to seek medical advice prior to significant 55 mmHg or 5559 mmHg with evidence of end-organ
deterioration. COPD exacerbations are common in damage). However, the role of oxygen therapy in patients
patients with moderate to severe COPD and may lead to with exertional desaturation, nocturnal hypoxaemia or
hospitalisation. Trials assessing the effects of action plans resting mild to moderate hypoxaemia is less clear. Recent
in COPD management have shown conflicting results, studies suggest an absence of long-term effects on breath-
with variable adjuncts to patient care in these trials lessness or quality of life from the use of ambulatory
likely contributors. Those with positive results, such as oxygen therapy in normoxaemic or mildly hypoxaemic
expedited exacerbation recovery and reduced hospital patients with COPD who desaturate with exertion, even
admissions, have included additional supports, such as though they may demonstrate small acute benefits
intensive education and case management.4345 In con- during laboratory-based exercise tests.51,52 Nonetheless,
trast, action plans with limited or no self-management occasional so-called n-of-1 trials may be of use in some
education and no case management have little benefi- individuals.52 Isolated nocturnal hypoxaemia is not
cial effect.46 In view of the healthcare cost implications uncommon in COPD patients, particularly during rapid
of COPD exacerbations, various models of self- eye movement sleep. However, it has not been shown to
management have been initiated in national healthcare lead to worse quality of life, daytime hypoxaemia or
systems, but the evidence for benefit has not been pulmonary hypertension. Limited studies have not con-
confirmed. Programmes may include self-management sistently shown beneficial effects in sleep quality, pulmo-
education about disease, optimisation of evidence-based nary haemodynamics or survival over 2 years with
medications, information and support from case man- nocturnal supplemental oxygen.5355 Similarly, patients
agers and institution of self-management principles. A with COPD and resting mild-to-moderate hypoxaemia
2007 Cochrane meta-analysis concluded that self- have not shown a survival benefit with domiciliary
management education in COPD was likely associated oxygen therapy. The currently recruiting US Long-term
with reduced hospital admissions and no detrimental Oxygen Treatment Trial (NCT00692198) may provide
effects, but determined that larger randomised con- more data regarding the effects of domiciliary oxygen in
trolled trials were required before clear recommenda- the latter patient subgroup.

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858 Internal Medicine Journal 2013 Royal Australasian College of Physicians
Advances in COPD

Non-invasive ventilation: air leaks) and mortality are significant.58 The majority of
acute versus stable patients with end-stage COPD are not suitable surgical
candidates because of their physiological fragility.
Non-invasive ventilation (NIV) is considered the standard Current selection guidelines for LVRS are largely based
of care for patients with acute exacerbations of COPD upon the results of the National Emphysema Treatment
associated with hypercapnic respiratory failure and aci- Trial inclusion criteria and outcome data and include
dosis. It has been shown to reduce mortality, need for bilateral, upper-lobe-predominant emphysema with sig-
intubation, treatment failure, treatment complications nificant hyperinflation and air trapping and a low
and length of hospital stay.22 Patients who survive after maximal workload after pulmonary rehabilitation.59
an episode of acute hypercapnic respiratory failure In order to obviate the need for surgery, there has been
treated with NIV are at high risk of readmission and considerable recent interest in the development of
life-threatening events during the following year. bronchoscopic techniques for lung volume reduction.
Although there are theoretical reasons why chronic NIV Modalities employed have included endobronchial valves
may benefit such patients, results from randomised con- or blockers, airway bypass, biologic sealants and airway
trolled trials have been conflicting. A systematic review implants. Endobronchial one-way valves block the
concluded there was no consistent clinically or statisti- airway leading to the targeted emphysematous lung.
cally significant effect of domiciliary NIV on lung func- Apart from allowing air to be vented and preventing
tion, gas exchange, exercise tolerance, respiratory muscle refilling, these valves also allow expulsion of mucus to
strength or sleep efficiency.56 However, many included minimise postobstructive infection. Modest improve-
studies had small sample sizes, included patients without ments in lung function, exercise tolerance and symptoms
significant hypercapnia, were of limited duration and/or have been demonstrated in selected patients with
used low levels of inspiratory pressure support. An Aus- advanced heterogenous emphysema using endo-
tralian study randomised 144 patients to receive home bronchial valves, although efficacy is variable and
NIV plus long-term home oxygen therapy versus oxygen adverse effects include increased risk of COPD exacerba-
alone.57 Home NIV was associated with an improvement tions, haemoptysis and pneumonia.60 Bronchoscopic
in survival up to 3.5 years, at the expense of worse thermal vapour ablation (BTVA) is a newer technique
quality of life. In summary, NIV may be a therapeutic that utilises heated water vapour to induce thermal reac-
option in stable COPD patients with chronic ventilatory tion and subsequent inflammatory response with perma-
failure, but further long-term randomised controlled nent fibrosis and atelectasis, leading to reduction in
trials are awaited. 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
Interventional therapy: surgery
that BTVA significantly improves lung function, symp-
and devices
toms and exercise tolerance.61 The most common adverse
In patients with very severe COPD who remain incapaci- effects of BTVA are lower respiratory events, pneumonia
tated by dyspnoea despite maximal therapy, various sur- and haemoptysis. These complex procedures require
gical approaches have been trialled. Currently available careful patient selection and assessment by a multidi-
surgical interventions include lung transplantation, lung sciplinary team at a specialised centre to ensure best
volume reduction surgery and bullectomy. Since the first outcomes.
successful clinical lung transplant in 1983, transplanta-
tion has become a treatment option for selected patients
Prognosis, palliative care and
with end-stage COPD, with improved survival. However,
advanced-care planning
transplantation is limited by donor availability, the need
for lifelong immunosuppression and its complications Lung function impairment is a strong predictor of mor-
and the development of chronic allograft dysfunction in tality; however, use of lung function alone to classify
the form of bronchiolitis obliterans. In patients with disease severity does not capture the multidimensional
emphysema, lung volume reduction surgery (LVRS) is nature of COPD. In patients with established COPD a
aimed at relieving the hyperinflation and gas trapping variety of indices has been proposed that enhance the
associated with inadequate lung emptying and its associ- ability to predict mortality. Degree of hyperinflation as
ated mechanical disadvantage. LVRS and bullectomy in measured by inspiratory capacity/total lung capacity ratio
selected patients have been shown to improve lung func- is more closely associated with all cause and COPD mor-
tion and exercise capacity in the long term, although tality than FEV1.62 The BODE index, incorporating body
perioperative morbidity (most commonly parenchymal mass index, degree of obstruction as measured by FEV1,

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Internal Medicine Journal 2013 Royal Australasian College of Physicians 859
McDonald & Khor

dyspnoea score and exercise capacity as measured by 6 functional status, increasing dependence on others, and
minutes walk distance into a common index, enhances advancing age.64 Ideally, end-of-life discussions, includ-
the ability to predict mortality.63 Further, the presence of ing resuscitation and intubation wishes, and advanced-
comorbid disease increases the risk of both hospitalisation care planning, including consideration of the conferment
and mortality. The predominant causes of mortality in of a medical enduring power of attorney, should occur in
patients with mild disease are cardiac disease and malig- an outpatient setting when the patients condition is
nancy, while as COPD severity increases, deaths due to relatively stable.
respiratory disease are increasingly common.
Severe dyspnoea, cough, fatigue, social isolation,
anxiety and depression are all features of late-stage COPD
Conclusion
that adversely impact quality of life. The COPD disease
course is often punctuated by recurrent exacerbations COPD is a common disease associated with significant
that may require hospitalisation and consideration of morbidity and mortality. Spirometry is key to its diagnosis
assisted ventilation. Hospitalisation for acute exacerba- and is required in order to avoid under- and
tion increases subsequent mortality risk. As the disease overtreatment. Smoking cessation and oxygen therapy in
progresses a more palliative approach to care may be those who are hypoxaemic may reduce mortality.
appropriate. Determining prognosis in end-stage COPD is Pharmacologic and non-pharmacologic therapy can
difficult; however, characteristics that should trigger dis- improve symptoms, quality of life and exercise capacity
cussions about a palliative approach to care, advanced- and, through their effects on reducing exacerbations,
care planning and end-of-life issues include FEV1 < 25%, have the potential to modify disease progression.
oxygen dependence, respiratory failure, heart failure or Comorbidities are common and require targeted
other comorbidities, weight loss or cachexia, decreased treatment.

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862 Internal Medicine Journal 2013 Royal Australasian College of Physicians