Professor David Halpin explores recent updates to the GOLD report and a stepwise approach to diagnosing patients who may have COPD, asthma, or both
Read this article to learn more about:
- the Global Initiative for Chronic Obstructive Lung Disease (GOLD)
- multidimensional assessment of chronic obstructive pulmonary disease (COPD)
- how assessments of symptoms and risk of exacerbations are used to guide pharmacotherapy
- diagnosis of the asthma–COPD overlap syndrome (ACOS).
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T he diagnosis and management of chronic obstructive pulmonary disease (COPD) remains a major health problem around the world. It is the fifth most common cause of death in England, killing more than 25,000 people a year. Apart from its effects on people living with the disease, COPD is a challenge for health services because it is the second biggest cause of emergency admissions to hospital in England.1
Guidelines available for COPD—an overview
The first British guidelines on the management of COPD were published by the British Thoracic Society (BTS) in 1997 and these were followed in 20042 by a guideline from NICE, which was updated and replaced in 2010.3 There are now many national guidelines that make broadly similar recommendations,4 but some of these, like the NICE guideline,3 have not been updated for some years; the focus in other guidelines is on only making recommendations supported by high-quality evidence, thereby limiting the scope to topics such as pharmacotherapy where randomised clinical trial data and meta-analyses are available.4 As a result, the clinically focused recommendations of the Global Initiative for Chronic Obstructive Lung Disease (GOLD)5 have been increasingly seen as the most relevant for clinical practice both around the world and also in the UK. For example, the local formulary recommendations in Devon are now based around GOLD recommendations rather than NICE guidance.6
GOLD global strategy
GOLD,5 which arose from a National Heart, Lung, and Blood Institute (NHLBI)/World Health Organization (WHO) workshop in 1998, aims to bring more attention to the prevention of COPD, to increase awareness of the condition, and to make recommendations about its management. In 2001, the GOLD programme released a consensus report, Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease.7 Since then the GOLD Science Committee has published annual updates addressing recently published data and modifying recommendations as necessary, with major reviews of the whole document in 2007 and 2011.8 A review of the major changes recommended in 2011 by GOLD when assessing COPD patients was published in Guidelines in Practice in 2014.9 The latest annual update to the GOLD document was published in December 2015 (updated January 2016, see reference 10 for these recent updates).10
This article will discuss the aspects of recent updates that are most relevant to clinical practice, including the publication of the GOLD 2015/16 appendix discussing the differential diagnosis of COPD and asthma, and the diagnosis and management of the so-called asthma–COPD overlap syndrome (ACOS).10
Multidimensional assessment of COPD
The latest updates to the GOLD strategy document (referred to in this article as 'the GOLD report')10 have not made any changes to the multidimensional assessment of COPD introduced in 2011 based on spirometry, symptoms, exacerbation risk, and presence of comorbidities. Spirometry, symptoms, and exacerbation risk are used to categorise patients into four groups: A, B, C, or D (see Figure 1, below) and the choice of initial pharmacological treatment is based on the group into which the patient falls.
An initial assessment of a patient's symptoms should be made using the modified British Medical Research Council's questionnaire (mMRC) or the COPD Assessment Test (CAT) score. On the basis of these assessments, patients are divided into those with few symptoms and those with a high level of symptoms.
Risk of exacerbations is then assessed either on the basis of worse lung function (as measured by the forced expiratory volume in 1 second [FEV1]) or by the frequency and severity of exacerbations in the past 12 months. The importance of exacerbations and, in particular, the impact of hospitalisation on long-term prognosis is highlighted in the 2016 update.10 The 5-year mortality rate following hospitalisation for COPD exacerbation is about 50%.10
Clinical features independently associated with poor outcome include older age, lower body mass index, comorbidities (e.g. cardiovascular disease, skeletal muscle dysfunction, metabolic syndrome, osteoporosis, depression, lung cancer), previous hospital admissions for COPD exacerbations, clinical severity of the index exacerbation, and need for long-term oxygen therapy at discharge.10
High-risk patients are those with:10
- FEV1 less than 50% predicted
- two or more exacerbations in the past year
- one or more hospitalisations with an exacerbation in the past year.
Patients can be assessed as high risk on the basis of lung function alone, exacerbations alone, or both.
Patients are allocated into one of the four groups on the basis of their symptoms and risk (see Figure 1, above):10
- A: few symptoms, better lung function
- B: more symptoms, better lung function
- C: few symptoms, poor lung function
- D: more symptoms, poor lung function.
Distribution of patients across groups and outcomes
Since the publication of this assessment scheme, large observational studies have been analysed to assess the distribution of COPD patients across the quadrants and to examine outcomes.11 The proportion of patients in different groups differs according to the way in which the cohorts were recruited: in a population identified by screening most fall into group A, while cohorts recruited mainly from secondary care have approximately equal numbers in groups A and D with smaller numbers in B and C. Most patients were assigned to groups C and D on the basis of a low FEV1, rather than because of a history of frequent exacerbations.11
Using the groups gives prognostic information, as might be expected: 5-year mortality was lowest in people in group A (just under 10% in a community sample) and highest in D (nearly 40%) but surprisingly similar (and intermediate) in B and C, whereas the incidence of exacerbations increases progressively from A to B to C to D. Comorbidities were particularly prevalent in the two 'high symptom' groups (B and D).11
Although the classification is recommended for initial assessment, the studies also looked at whether patients changed group over time. Patients in groups A or D tended to remain in the same group over time, whereas those in B or C changed substantially, mainly as a result of disease progression (developing more symptoms or exacerbations) or response to therapy.11
Assessment in this way has been seen as difficult or time-consuming by some primary care clinicians, but is considerably simpler than multidimensional cardiovascular risk assessment such as QRISK® 2;12 it also moves towards the concept introduced in NICE CG101 that assessment of patients should, importantly, be multidimensional and not rely solely on the degree of FEV1 impairment.3
The assessments of symptoms and risk of exacerbations are used to guide pharmacotherapy. Short-acting bronchodilators can be prescribed for people with few symptoms and low risk (Group A)10 but most patients require treatment with long-acting bronchodilators, which improve symptoms and reduce exacerbation rates13,14 as well as improving lung function and exercise capacity.
There are now a number of long-acting bronchodilators available for use in COPD (see Table 1, below). Beta agonists and antimuscarinics act through different mechanisms and are both effective in COPD as monotherapy and in combination.15
|Long-acting antimuscarinics (LAMAs)||Long-acting beta agonists (LABAs)|
Long-acting antimuscarinics (LAMAs) are superior to long-acting beta agonists (LABAs) as monotherapy.10,16,17 Once-daily tiotropium, administered via a dry powder or soft mist inhaler, has been used for many years to treat COPD effectively10,18 and has an excellent safety record.19 Glycopyrronium and umeclidinium are also once-daily LAMAs and aclidinium is a twice-daily LAMA; all these drugs are administered using dry-powder inhalers.20 These newer LAMAs appear to have similar effects on lung function to tiotropium,21–23 but do not appear as effective at reducing exacerbations and do not have as extensive safety data.
One of the main recent developments in the pharmacotherapy of COPD has been the introduction of combination inhalers containing both a LABA and a LAMA. The GOLD 2016 report has not updated the assessment that these LABA/LAMA combinations significantly improve lung function compared with monotherapy but that the benefits to patient-reported outcomes, such as breathlessness, are limited.10
More evidence on the effects of these combinations has been published in the last few years and, in line with earlier studies, shows large improvements in lung function with combination therapy compared with monotherapy, as well as a reduction in breathlessness and improvement in quality of life for significantly more people.24 It is suggested by GOLD that these combinations can be used as alternatives to LAMA in people in Groups B, C, and D, but GOLD does not yet give guidance on which patients should have combination therapy as their initial treatment rather than after a trial of monotherapy.10
Dual therapy, inhaled corticosteroids, and combination therapy
For patients who remain or become frequent exacerbators despite treatment with a LAMA, GOLD recommends that these individuals are either stepped up to dual bronchodilator therapy or that an inhaled corticosteroid (ICS)/LABA combination therapy is added. The ICS/LABA combination should only be used only in GOLD group C and D patients with a history of exacerbations, where the benefits of these drugs outweigh the risk of long-term side-effects, particularly osteoporosis, diabetes, and pneumonia.25
In practice, ICSs have been prescribed to many patients who do not meet these criteria and the 2016 update to the GOLD report10 addresses the issue of ICS withdrawal. It recognises that 'withdrawal from treatment with inhaled corticosteroids may lead to exacerbations in some patients'10 but also that 'in another study with severe and very severe COPD patients, inhaled corticosteroids could be gradually withdrawn over a three-month period without increasing the medium term risk of exacerbations, although lung function deteriorated significantly.'10
When withdrawing ICS, great care is needed to ensure that patients do not have asthma with fixed airflow obstruction—misdiagnosed as COPD or as part of the asthma–COPD overlap syndrome (see below).
Asthma–COPD overlap syndrome
In 2015/16, both the GOLD10 and Global Initiative for Asthma (GINA)26 reports included a section discussing the differential diagnosis of COPD and asthma and the diagnosis and management of the so-called asthma–COPD overlap syndrome (ACOS).
Some patients who present with chronic respiratory symptoms, particularly older patients, have diagnoses and/or features of both asthma and COPD, and are found to have airflow limitation that is not completely reversible after bronchodilatation.27–29 Some have an unequivocal history of asthma that has been poorly controlled and has resulted in fixed airflow obstruction, but which remains asthma. A small group of patients, however, have risk factors for and clinical features of both diseases and the concept of an 'overlap' syndrome has been proposed.10 These patients experience frequent exacerbations,31 have a worse quality of life, a more rapid decline in lung function, and higher mortality;28,30 they also consume considerably more healthcare resources31 than patients with either asthma or COPD alone.
Prevalence of asthma–COPD overlap syndrome
The true prevalence of ACOS is difficult to determine because different studies have used different diagnostic criteria. Using the loosest definition of ACOS, which includes people who do not have fully reversible airflow obstruction in the context of an obvious diagnosis of asthma, the prevalence has been stated at over 25% of people with asthma;32 in people with COPD with significant bronchodilator responses, the prevalence of ACOS in COPD has been stated to be 56%.33 With a more sensible definition, however, which includes people with clinical features of both asthma and COPD, exposure to a risk factor for COPD, and where a firm diagnosis of asthma or COPD cannot be made, the prevalence is around 10–15% of people with airways disease.34,35 Asthma–COPD overlap syndrome is thus uncommon and in the overwhelming majority of patients a definite diagnosis of either asthma or COPD can and should be made.
Stepwise approach to diagnosis of chronic airways disease
The ACOS section in the GOLD report proposes a stepwise approach to diagnosing people with chronic airways disease (see Box 1, below).10
Box 1: Stepwise approach to diagnosis of patients with respiratory symptoms10
- Step 1: Does the patient have chronic airways disease?
- Step 2: The syndromic diagnosis of asthma, COPD, and ACOS in an adult patient
- Step 3: Spirometry
- Step 4: Commence initial therapy
- Step 5: Referral for specialised investigations (if necessary).
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. Updated 2016. GOLD, 2016.
Reproduced with permission
Step 1: Does the patient have chronic airways disease?
As with most medical conditions, making an accurate diagnosis depends on taking a good and detailed medical history (see Box 2, below) to:
- ascertain exposure to risk factors
- characterise the symptoms (including provoking and relieving factors and variability)
- identify features that make conditions such as cardiac failure more likely causes of the symptoms.
Box 2: Features in the history suggesting that chronic airways disease is the cause of the symptoms10
- History of chronic or recurrent cough, sputum production, dyspnoea, or wheezing; or repeated acute lower respiratory tract infections
- Report of a previous doctor diagnosis of asthma or COPD
- History of prior treatment with inhaled medications
- History of smoking tobacco and/or other substances
- Exposure to environmental hazards (e.g. occupational or domestic exposures to airborne pollutants).
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. Updated 2016. GOLD, 2016.
Reproduced with permission
A physical examination should then be undertaken to look for features of airways disease such as hyperinflation and wheeze and exclude other causes of the symptoms.10 Investigations such as a chest radiograph may show features suggestive of chronic airways disease (e.g. hyperinflation and flattening of the diaphragm) or features suggestive of other conditions (e.g. pulmonary fibrosis or bronchiectasis). Increasing numbers of patients have had computerised tomography (CT) scans of their thorax for unrelated symptoms, such as chest pain, and these may also give useful information to support or refute chronic airways disease as a cause of symptoms.10
Step 2: The syndromic diagnosis of asthma, COPD, and ACOS in an adult patient
On the basis of the history and examination and any relevant investigations, a firm diagnosis of asthma or COPD can be made in most patients. In the small number of patients in whom this is not possible the GOLD report10 proposes considering the number of features that are helpful in distinguishing between asthma and COPD in clinical practice and counting the number that favour a diagnosis of asthma and the number that favour a diagnosis of COPD (see Table 2, below). The text states that having three or more of the features listed for either asthma or for COPD, in the absence of those for the alternative diagnosis, provides a strong likelihood of a correct diagnosis of asthma or of COPD.
|Features: if present suggest||Asthma||COPD|
|Age of onset||
|Pattern of respiratory symptoms||
|Lung function between symptoms||
|Past history or family history||
|For a patient, count the number of check boxes in each column. If three or more boxes are checked for either asthma or COPD, the patient is likely to have that disease. If there are similar numbers of checked boxes in each column, the diagnosis of ACOS should be considered.|
|FEV1 =forced expiratory volume in 1 second; FVC=forced vital capacity; COPD=chronic obstructive pulmonary disease; ACOS=asthma–COPD overlap syndrome|
|Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. Updated 2016. GOLD, 2016. Available at: www.goldcopd.org
Reproduced with permission
The report also points out, however, that the absence of any of these typical features has less predictive value, and does not rule out the diagnosis of either disease. It gives the example that a history of allergies increases the likelihood that respiratory symptoms are due to asthma, but such a history is not essential for the diagnosis of asthma since non-allergic asthma is a well-recognised asthma phenotype.10 When a patient has similar numbers of features of both asthma and COPD, the diagnosis of ACOS should be considered—but it is important to realise that there is no single diagnostic test or pathognomonic features to confirm the diagnosis.
The report acknowledges that in clinical practice, diagnoses are often made based on the weight of evidence, provided that there are no features that would clearly make the diagnosis untenable.10 A trial of treatments should be based on the likely diagnosis; where there is still significant doubt, a safety-first approach should be adopted and treatment for the asthma should be offered as this could be life saving.10
Step 3: Spirometry
Spirometry is essential for the assessment of patients with suspected chronic disease of the airways. It should be performed as soon as a diagnosis of chronic airflow limitation is suspected.10 Spirometry confirms chronic airflow limitation but is of almost no value in distinguishing between asthma with fixed airflow obstruction, COPD, and ACOS, even taking into account pre- and post-bronchodilator values. Some people with asthma have no or minimal response to short-acting bronchodilators36 while some people with COPD show a marked response.37
If asthma is suspected, repeated twice-daily measurement of peak expiratory flow (PEF) over a period of 1–2 weeks may help to confirm the diagnosis if marked (for example, greater than 20%)3,10 diurnal or day-to-day variability is shown. A normal PEF, however, does not rule out either asthma or COPD and a high level of variability in PEF may also be found in ACOS.10
Step 4: Commence initial therapy
If a diagnosis of asthma or COPD is made, patients should be managed according to local guidelines or to the GINA26 or GOLD10 reports. If ACOS seems to be the likely diagnosis, it is recommended that the initial treatment should be based on asthma guidelines, using low- or moderate-dose ICS and a LABA or LAMA, until the response to treatment or further investigations clarify the diagnosis. This approach recognises the pivotal role of ICS in preventing morbidity and even death in patients with uncontrolled asthma symptoms, for whom even seemingly 'mild' symptoms (compared with those of moderate or severe COPD) might indicate significant risk of a life-threatening attack.10 For this reason, LABA or LAMA monotherapy should not be used in people with ACOS.
Step 5: Referral for specialised investigations (if necessary)
If patients have persistent symptoms and/or exacerbations despite treatment or if there are clinical features to suggest alternative diagnosis (e.g. bronchiectasis, pulmonary fibrosis, pulmonary hypertension, or cardiovascular diseases) patients should be referred for further evaluation. Patients should also be referred if they have a clear diagnosis but also have atypical or additional symptoms or signs (e.g. haemoptysis, significant weight loss, or night sweats) that suggest an additional diagnosis.
The GINA–GOLD report on ACOS38 points out that our understanding of ACOS is at a very preliminary stage and most evidence about managing people with chronic airflow limitation comes from studies that have used specific entry criteria to exclude people with asthma from COPD studies, and vice versa, with the result that people with ACOS have been excluded from all studies of pharmacotherapy for chronic airway disease.
There is an obvious need for more research on the management of ACOS. Further work is needed to inform the development of evidence-based diagnostic definitions, and studies are needed on people with ACOS to define optimal management.
There were minor changes to the recommendations on COPD management in the 2015 and 2016 updates to the GOLD report. It continues to emphasise the importance of the multidimensional assessment of COPD, introduced in 2011, based on spirometry, symptoms, exacerbation risk, and presence of comorbidities; however, in 2015 a section discussing the differential diagnosis of COPD and asthma and the diagnosis and management of the so-called asthma–COPD overlap syndrome (ACOS) was added.
Long-acting bronchodilators remain the mainstay of pharmacotherapy in COPD and although there is growing evidence about the efficacy of LABA/LAMA combinations, the place of these drugs in the management algorithm has not yet been addressed by GOLD. Inhaled corticosteroids have a limited place and the updated GOLD report states that ICS can be withdrawn, if it has been prescribed inappropriately, without increasing the medium-term risk of exacerbations.
A much more extensive revision of the GOLD report is due to be published in 2017.
- There were minor changes to the recommendations on COPD management in the 2015 and 2016 updates to the GOLD Report.
- Multidimensional assessment of COPD based on spirometry, symptoms, exacerbation risk, and presence of comorbidities remains essential
- Long-acting bronchodilators remain the mainstay of pharmacotherapy
- Inhaled corticosteroids have a limited place in the management of COPD and in most cases can be withdrawn, if they have been prescribed inappropriately, without increasing the medium-term risk of exacerbations
- Most patients with chronic airways disease can be confidently diagnosed with COPD or asthma and managed according to relevant guidelines
- In a small proportion of patients, there are features of both COPD and asthma and they can be considered to have the so-called asthma–COPD overlap syndrome (ACOS)
- Patients with ACOS should be managed with ICS at asthma doses together with a long-acting bronchodilator
- A more extensive revision of the GOLD Report will be published in 2017.
COPD=chronic obstructive pulmonary disease; GOLD=Global Initiative for Chronic Obstructive Lung Disease; ACOS=asthma–COPD overlap syndrome; ICS=inhaled corticosteroid
GP commissioning messages
written by Dr David Jenner, GP, Cullompton, Devon
- The 2015/16 GOLD recommendations should inform local management of COPD until NICE Clinical Guideline 101 has been reviewed and updated
- The GOLD recommendations are likely to identify many patients currently prescribed inhaled corticosteroids who may not necessarily need them:
- withdrawal of steroids, however, brings some risk of increased exacerbations in patients who have been poorly diagnosed and who in reality have asthma or ACOS, so close monitoring will be required
- may wish to support practices with extra funding or specialist nurses to monitor patients whose steroids have been withdrawn, bringing possible savings in prescribing budgets
- should identify the licensed preparations for combination therapies and list them in formularies alongside their licensed indications and acquisition costs, as these costs now vary considerably
- could run education events for practice nurse leads on using multidimensional assessment, which is likely to reduce inappropriate prescribing of inhaled steroids and optimise bronchodilator therapy.
GOLD=Global Initiative for Chronic Obstructive Lung Disease; COPD= chronic obstructive pulmonary disease; ACOS=asthma–COPD overlap syndrome
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