The GOLD 2011 classification (1) is based on a system of symptom and risk assessment and not just FEV1 alone. The new strategy guide emphasises the importance of patient assessment and recommends management strategies for the individual patient incorporating symptoms, risk of future exacerbations and the degree of airflow limitation using spirometry. The assessment places emphasis on impact of the disease and the future risk of disease progression and highlights the importance of exacerbations and comorbidities in the management of COPD. In a departure from the previous version, a staging system for COPD based on FEV1 is no longer advocated; instead COPD is simply graded as mild, moderate, severe and very severe split at 80 per cent, 50 per cent and 30 per cent of the predicted value of FEV1. Exacerbation risk is determined through exacerbation history and spirometry: an individual who has had two or more exacerbations in a year and/or an FEV1 less than 50 per cent of the predicted value is considered to be at high risk of future exacerbations. Symptoms can be assessed through the COPD Assessment Test (CAT) or the Medical Research Council (MRC) Breathlessness scale. Based on this combined assessment, four patient types can be identified as shown in Figure 1.4.
There are specific treatment recommendations based on the category the patient fits, the objective being individualised treatment for each patient depending on where they are placed on the GOLD assessment grid. Importantly these are not recommendations based on primary clinical trial evidence, as no trials have yet used this grouping; instead it is a consensus of expert opinion.
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Figure 1.4 The GOLD 2011 assessment grid
1.6.1 Assessment of Risk – Based on spirometry
Table 1.7 shows the assessment of risk based on spirometry.
CAT<10 or mMRC 0-1 CAT ≥ 10 or mMRC ≥ 2
Type A individual has low risk and few symptoms; type B is a low risk individual but with more symptoms, type C defines one who is at high risk but with less symptoms and type D is one who is at high risk and has many symptoms.
(A)
(B)
(C)
(D)
GOLD
STAGES
EXAC FREQ
2
1
4
3
1
0
≥2
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In patients with FEV1/FVC < 0.7
GOLD 1 Mild FEV1 > 80% predicted
GOLD 2 Moderate 50% ≤ FEV1 < 80%
GOLD 3 Severe 30% ≤ FEV1 < 50%
GOLD 4 Very severe FEV1 < 30% predicted
Table 1.7 Spirometric assessment of Risk categories in COPD
For purposes of this assessment, GOLD 1 and 2 categories are classified as lesser risk and those in categories 3 and 4 are at higher risk. However the relation between FEV1, symptoms and impact on quality of life is weak. It has been demonstrated that within any given category, there is a wide variation with people having well preserved to poor health status (81). As a result a formal symptomatic assessment is also required.
Data from 3 large prospective studies (TORCH, UPLIFT, and ECLIPSE) demonstrated that as the previous GOLD stage worsened, the exacerbation rate increased, hospitalisation rate increased and mortality increased. This was built into the current GOLD assessment taking a cut off point between GOLD 2 and GOLD 3. It has to be borne in mind that this is a population based estimate i.e. a probability estimate like blood pressure (BP); increased BP increases the risk of stroke and myocardial infarction, but knowing an individual patient’s BP does not tell you whether or when that patient is going to have a stroke. Similarly knowing an individual’s FEV1 helps in knowing the severity of airflow limitation but on its own it does not predict the severity of symptoms or whether the symptoms would progress or remain static.
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1.6.2 Assessment of Risk – Based on Exacerbation History
Exacerbations are very important in the natural progression of COPD. They result in significant morbidity and mortality and have an adverse impact on lung function (141). Exacerbation rates vary widely among patients. The ECLIPSE study demonstrated that about 20% of patients in GOLD category 2 (Moderate airflow limitation) had > 2 exacerbations. It also showed that the rate of exacerbations per year does help to predict to a large extent the number of exacerbations in the subsequent years (81). Thus it was felt that exacerbation history had to be taken into account in addition to the risk estimated from spirometry to assess the risk more fully.
Exacerbations may accelerate decline in lung function and are directly responsible for hospitalisations, death and poor prognosis in COPD (188). Hence the risk estimate can be based on a combination of spirometric risk and risk arising from exacerbation history. Where it was felt that the risk from one of these parameters is higher it was decided that the patients should be assigned to the category with the higher risk. This was justified based on the purpose of the classification i.e. to identify patients with poorer prognosis.
This raises an interesting question- We have two risk estimates. Which do we use? The purpose is to identify patients who are at greatest risk and hence we should use the highest risk estimate. This would help identify patients with GOLD 1 or 2 but with >2 exacerbations – that would move them up from A to C and from B to D categories. It has been shown that about 22% with moderate COPD (GOLD stage 2) had frequent (≥ 2) exacerbations. It is important to recognise these patients for management options to lower exacerbations.
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1.6.3 Treatment recommendations
The GOLD strategy also recommends treatment options based on these 4 categories shown in Fig 1.4 and are detailed in table 1.8 below.
PATIENT GROUP
FIRST CHOICE SECOND CHOICE ALTERNATIVE CHOICE
A SABA prn or SAMA prn LAMA or LABA or SABA+ SAMA THEOPHYLLINE
B LAMA or LABA LAMA+ LABA SABA ± SAMA
C ICS + LABA/LAMA LAMA+LABA PDE - 4 inhibitor
SABA ± SAMA Theophylline
D ICS + LABA/LAMA ICS + LAMA
or ICS+LABA+LAMA
or LAMA + LABA
or
LAMA + PDE-4 inhibitor
Carbocysteine SABA ± SAMA Theophylline
Table 1.8 GOLD 2011 treatment recommendations
SABA Short acting bronchodilator SAMA Short acting muscarinic antagonist LABA Long acting bronchodilator LAMA Long acting muscarinic antagonist ICS Inhaled corticosteroid PDE4 Phosphodiesterase 4
Therapy in COPD is mainly directed at airflow obstruction and inflammation, with additional effects on exacerbations, although it is not known if this influences infective or non-infective aetiology. Thus short and long acting bronchodilators, acting via beta adrenoceptors (β2 agonists) and anticholinergic pathways are recommended to be used in a stepwise manner, with the addition of inhaled steroids later in the disease. It has been suggested that they should be combined with a long acting β2 agonist when FEV1 is below 50% of the predicted
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normal value, and when the patient is experiencing regular exacerbations (173). Many of the newer treatments for COPD have been directed at individual components of inflammation, given its’ importance in pathogenesis. However most, such as anti-TNFα, have been disappointing (189).
Peripheral blood eosinophilia has been shown to be a surrogate marker for eosinophilic inflammation in COPD (153) and a peripheral blood eosinophilia >2% has been shown to indicate response to corticosteroid therapy in outpatient management of exacerbations of COPD (190).
1.6.4 Controversies of the new strategy
The new classification system has not been without its controversies. The strategy assumed that an mMRC threshold of 1 equates to a CAT score of 10. There is a lack of convincing evidence to support this assumption; this threshold has not been independently validated yet nor has the utility in predicting clinical outcome. It has also not been validated in sub-groups of COPD patients, such as those with AATD. Despite this there is agreement that the new assessment system represents an important step forward towards personalised medicine in COPD and studies to validate its assumptions and predictive abilities are needed for future refinement.