Professor David Halpin provides an overview of new recommendations in the latest revision to the GOLD COPD strategy

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Professor David Halpin

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Read this article to learn more about:

  • strategies for initial and follow-up treatment of chronic obstructive pulmonary disease (COPD)
  • how to escalate and de-escalate pharmacotherapy
  • using blood eosinophil count as a biomarker to guide treatment choice in COPD.

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Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality in the UK. In November 2018, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) committee published its 2019 strategy on the diagnosis, management, and prevention of COPD.1 The report builds on the changes introduced in the last major update in 2017, but makes significant revisions to the pharmacological treatment recommendations.

The 2019 report continues to recommend that patients are diagnosed and assessed as described in the 2017 version. A diagnosis of COPD is based on the presence of symptoms and airflow obstruction demonstrated by a post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio of less than 0.7 on spirometry.1 The goals of assessment are to determine the level of airflow limitation, the impact of the disease on the patient’s health status, and the risk of future events (such as exacerbations, hospital admissions, or death). To achieve these goals, the 2019 GOLD report recommends that assessment of people with COPD must consider the following aspects of the disease separately:1

  • presence and severity of the spirometric abnormality
  • current nature and magnitude of the patient’s symptoms
  • history of moderate and severe exacerbations and future risk
  • presence of co-morbidities. 

The degree of FEV1 impairment, expressed as a percentage of the predicted value, is used to determine the GOLD stage (1 to 4). The severity of symptoms (as determined by the Modified Medical Research Council breathlessness score [mMRC] or the COPD Assessment Test [CATTM]) and the risk of exacerbations (based on the number of moderate or severe exacerbations in the previous year) are used to determine the patient’s GOLD group (A to D) (see Figure 1). The 2019 report emphasises that this assessment of symptom severity and exacerbation risk is recommended only as a basis for determining initial therapy and is not designed for reassessing patients during follow up.1

For the first time, GOLD has introduced the use of blood eosinophil count as a circulating biomarker to help guide treatment choice. There has been considerable interest in whether or not eosinophils can be used to predict clinical outcomes, such as the risk of exacerbations and whether they can predict the likelihood of benefit or harm from treatment with inhaled corticosteroids (ICS).2 Eosinophilic airway inflammation is present in a subset of patients with COPD and blood eosinophil counts have been used as a practical biomarker of eosinophilic airway inflammation in patients with COPD.3

Studies have shown that blood eosinophil counts are not reliable as predictors of the risk of exacerbations, but analysis of recent clinical trials has shown that eosinophil counts are consistently predictive of the efficacy of ICS in reducing exacerbations. Low eosinophil counts are predictive of a higher risk of developing pneumonia. The relationship between blood eosinophil count and both the likelihood of benefit and the risk of harm are continuous,4 but it is now possible to propose thresholds that can be used as guides in clinical practice and this approach has been adopted in the 2019 GOLD report.


Figure 1: Assessment of patients with COPD1

Source: Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. GOLD, 2019. Reproduced with permission.

FEV1 =forced expiratory volume in 1 second; FVC=forced vital capacity; GOLD=Global Initiative for Chronic Obstructive Lung Disease; mMRC=Modified Medical Research Council; CAT=COPD Assessment Test

Initial pharmacotherapy

The 2017 version of the report made recommendations on initial treatment options based on the patient’s GOLD group, A, B, C, or D. Each GOLD group featured a ‘preferred treatment pathway’ to guide clinicians on initial treatment choice and how to escalate/de-escalate treatment; however, the implication of this was that each pathway only applied to a patient whose initial assessment had placed them in that group. There was no indication of what to do if a patient’s clinical profile changed, for example, if for the first time they had several exacerbations. The 2019 report has attempted to address this by clearly separating recommendations for initial therapy (which have now been simplified), from recommendations about how to escalate or de-escalate therapy based on changes in the patient’s breathlessness or exacerbation frequency. The GOLD committee developed these revised algorithms on the best evidence currently available, but recognised that there are still significant gaps in the evidence meaning that some of the new recommendations are based on expert consensus.1

GOLD COPD strategy initial pharmacological treatment

Figure 2: GOLD COPD strategy initial pharmacological treatment1

Source: Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. GOLD, 2019. Reproduced with permission.

LAMA=long-acting muscarinic antagonist; LABA=long-acting beta agonist; ICS=inhaled corticosteroids; mMRC=Modified Medical Research Council; CAT=COPD Assessment Test

Figure 2 shows the recommended initial pharmacotherapy for patients in groups A to D. Bronchodilators are still the recommended initial treatment for patients in groups A, B, and C. For patients in group A this may be either a short- or long-acting bronchodilator depending on the intensity and frequency of symptoms, but for patients in groups B and C it should be a long-acting drug; a long-acting muscarinic antagonist (LAMA) is recommended in group C because of their superior efficacy at reducing the risk of exacerbations.

The choice of initial therapy for patients in group D, who are both symptomatic and at risk of exacerbations, depends on the intensity of symptoms and may also be influenced by the blood eosinophil count. A LAMA is the recommended initial therapy unless the patient is highly symptomatic (e.g. CAT score >20), in which case dual bronchodilator therapy with a LAMA plus a long-acting beta agonist (LABA) is the recommended option. If patients in group D have a blood eosinophil count of ≥300 cells/μl, initial therapy with a LABA+ICS can also be considered.1

Review, assess, adjust

Following treatment initiation, GOLD recommends that patients should be reassessed to determine:1

  • whether the treatment goals (e.g. reduction of symptoms and future risk of exacerbations) have been achieved and if not
  • whether there are any correctable barriers to successful treatment such as poor inhaler technique or poor adherence (see Figure 3).

At the patient’s review, it is also essential to consider non-pharmacological interventions such as pulmonary rehabilitation and smoking cessation.1

GOLD COPD management cycle

Figure 3: Review and management cycle1

Source: Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. GOLD, 2019. Reproduced with permission.

Escalation and de-escalation of pharmacotherapy

If the response to initial therapy is sufficient, treatment should be continued. However, if the patient is continuing to have problems, GOLD has introduced a new algorithm providing recommendations on how to modify the therapy to deal with persistent dyspnoea, continuing exacerbations, or both (see Figure 4). Importantly, this algorithm applies to any patient who is already taking maintenance treatment(s) irrespective of the GOLD group allocated at treatment initiation.1

This algorithm requires the clinician to identify what the predominant treatable trait is (dyspnoea or exacerbations) and what therapy the patient is currently receiving. The clinician should then use the relevant pathway based on the patient’s predominant trait. If the patient is experiencing both dyspnoea and exacerbations, the exacerbations pathway should be used.1

GOLD COPD strategy follow up pharmacological treatment

Figure 4: Follow-up pharmacological treatment1

Source: Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. GOLD, 2019. Reproduced with permission.

LABA=long-acting beta agonist; LAMA=long-acting muscarinic antagonist; ICS=inhaled corticosteroids; FEV1 =forced expiratory volume in 1 second

Dyspnoea pathway

If a patient continues to experience dyspnoea while on LABA+ICS therapy, GOLD recommends escalating their treatment to LABA+LAMA+ICS. If a patient is taking LAMA monotherapy and still experiences breathlessness, their treatment should be escalated to dual bronchodilator therapy with LABA+LAMA. If a patient is currently on LABA+LAMA and is still breathless, GOLD recommends considering changing to a different inhaler device or different molecules, as well as undertaking investigations to look for other causes of breathlessness such as heart failure or atrial fibrillation.1

Exacerbation pathway

For patients with persistent exacerbations on LABA or LAMA monotherapy, GOLD recommends escalating to either LABA+LAMA or LABA+ICS depending on the patient’s blood eosinophil count. Escalation to LABA+ICS therapy is recommended if the patient’s blood eosinophil count is:1

  • ≥300 cells/µl or
  • ≥100 cells/µl and the patient has had at least two moderate exacerbations (i.e. requiring treatment with antibiotics and/or prednisolone) or one severe exacerbation (i.e. hospitalised). 

Recent trial data have shown that in this population LABA+ICS is more effective than LABA+LAMA at preventing exacerbations.1 For patients who do not fit into the above criteria, escalation to LABA+LAMA is recommended because there is very little likelihood of benefit from treatment with ICS in this group, and there is evidence that they may be at greater risk of developing pneumonia. If the patient is already on LABA+ICS and is continuing to have exacerbations then the recommended escalation is to triple therapy with LABA+LAMA+ICS.

If the patient is on LABA+LAMA the recommended escalation again depends on the blood eosinophil count. If it is less than 100 cells/µl there is a very low likelihood of a beneficial response to ICS, and therefore the recommended escalation route is either regular macrolide therapy or adding a phosphodiesterase-4 inhibitor according to the patient’s phenotype. If the eosinophil count is ≥100 cells/µl then escalation to triple therapy is recommended.1

De-escalation of treatment

De-escalation strategies are currently limited to patients who are taking ICS. De-escalation of ICS can be considered if:1

  • the patient experiences pneumonia
  • there was an inappropriate indication for the ICS when they were first prescribed
  • there was a lack of response (i.e. no change in the frequency of exacerbations following the introduction of ICS therapy). 

De-escalation may also be considered in patients with COPD receiving treatment who return with resolution of some symptoms that subsequently may require less therapy. For patients who have had their treatment de-escalated, it is important to monitor them under close medical supervision to ensure they do not deteriorate as a result of the changes.1

Other updates

Several other updates have been included in the 2019 GOLD report and a couple of important clarifications were made in the 2018 report. The 2018 iteration included a recommendation that a diagnosis of airflow obstruction should not be made on the basis of a single spirometry result if the initial result showed a FEV1/FVC ratio that was close to the diagnostic threshold of 0.7. If the ratio is between 0.6 and 0.8, spirometry should be repeated on a separate occasion, as in some cases the ratio may change as a result of biological variation when measured at a later interval.5,6 If the initial post-bronchodilator FEV1/FVC ratio is less than 0.6 it is very unlikely to rise above 0.7 spontaneously.5 The 2018 report also clarified that it is the frequency of moderate and severe exacerbations, not mild exacerbations, that should be considered when assigning a patient to a GOLD group.

The 2019 report also updates the evidence and recommendations on non-pharmacological therapy and makes recommendations, based on the patient’s GOLD group, on the use of these approaches as part of initial management (see Table 1). Non-pharmacological approaches, including smoking cessation and pulmonary rehabilitation, are essential components of COPD management and often have a greater impact than drug therapy. Therefore, they should be offered to all patients alongside pharmacological therapy.

Table 1: Non-pharmacological therapy1
Patient groupEssentialRecommendedDepending on local guidelines

Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. GOLD, 2019.Reproduced with permission.


Smoking cessation (can include pharmacological treatment)

Physical activity

Flu vaccination

Pneumococcal vaccination


Smoking cessation (can include pharmacological treatment)

Pulmonary rehabilitation

Physical activity

Flu vaccination

Pneumococcal vaccination


The new recommendations in the 2019 GOLD report represent important advances in the development of personalised pharmacotherapy for patients with COPD. A combination of clinical and laboratory biomarkers are now used to determine the optimum initial treatment, and clarification is given on how therapy should be modified in the light of regular reviews of treatment response. In December 2018, NICE published another partial update to NICE Guideline 115 on Chronic obstructive pulmonary disease in over 16s: diagnosis and management.7 This updated several aspects of COPD management including the use of prophylactic antibiotics and oxygen, managing pulmonary hypertension and cor pulmonale, the role of lung volume reduction procedures, and self-management and exacerbation plans. It also contains updated recommendations and an algorithm on the use of inhaled therapies. The NICE updates do not contradict the recommendations in the GOLD report and emphasise the central role of long-acting bronchodilators; however, they are more simplistic in their approach to treatment escalation and they do not use the blood eosinophil count to guide the use of ICS. It seems likely that the more practically useful recommendations in the 2019 GOLD report will continue to be the main reference for clinicians in the UK.

Professor David Halpin

Consultant Physician, Royal Devon and Exeter Hospital

Member of the GOLD Board of Directors and Science Committee

Key points

  • Significant changes have been made to the recommendations on pharmacotherapy for COPD in the 2019 GOLD report
  • Multidimensional assessment of COPD based on spirometry, symptoms, exacerbation risk, and presence of co-morbidities remains essential
  • Initial and follow-up pharmacotherapy are now presented in two separate algorithms for clarity
  • Initial therapy is based on the patient’s GOLD group and includes non-pharmacological as well as pharmacological approaches
  • After maintenance therapy has been prescribed, patients should be reviewed to determine their response to the treatment. The review should include assessment of inhaler technique and compliance
  • Patients who remain breathless or who continue to experience exacerbations should have their therapy escalated:
    • the new therapy is determined by both their current therapy and whether it is dyspnoea or exacerbations (or both) that are problematic
  • Long-acting bronchodilators remain the mainstay of pharmacotherapy
  • It is recommended that the use of ICS is guided by the blood eosinophil count.

COPD=chronic obstructive pulmonary disease; GOLD=Global Initiative for Chronic Obstructive Lung Disease; ICS=inhaled corticosteroids

Implementation actions for clinical pharmacists in general practice

written by Gupinder Syan, Training and Clinical Outcomes Manager, Soar Beyond Ltd

The following implementation actions are designed to support clinical pharmacists in general practice with implementing the guidance at a practice level. 

  • Agree which patient groups are within your scope of competence to review.
    • start with one cohort and build on this once your experience and confidence grows e.g. start with GOLD group A patients (on bronchodilators), then move on to patients in group B, C, and D
  • Ensure that your teams know which patient groups you are reviewing so that appropriate patients are booked in
  • Co-ordinate with other HCPs who also contribute to COPD clinics to ensure that joint working is effective and streamlined
  • Assess your own needs—
    • is there a practice need for you to undergo spirometry training?
    • do you know how to assess the severity of symptoms?
    • do you know how to perform mMRC breathlessness scoring, perform CAT scoring, assess risk of exacerbations, and assess GOLD grouping?
    • do you know the red flags and differential diagnoses, taking into account co-morbidities?
    • do you have the appropriate equipment to check inhaler technique?
    • are you able to request blood eosinophil counts in your practice and use these to help guide treatment options?

Deliver the following in your clinics:

  • Review symptoms (dyspnoea pathway), number of exacerbations (exacerbation pathway)
  • Assess  inhaler technique and adherence, non-pharmacological approaches (including referral to pulmonary rehabilitation and self-management education, smoking cessation advice, flu and pneumococcal vaccinations)
  • Adjust LABA/LAMA/ICS/regular macrolide/phosphodiesterase-4 inhibitor based on eosinophil counts (escalation pathway), switch inhaler devices or molecules, de-escalate ICS and monitor for symptom effects (de-escalation pathway)
  • Agree next steps and decision making with patient to ensure a patient-centred approach is adopted
  • Evaluate  the outcomes. Show how many patients in each cohort you have seen and the patient interventions made (e.g. escalation, de-escalation, device changes, inhaler technique improvements), contribution to QOF income (e.g. vaccinations administered, COPD QOF targets met), and improvement to practice outcomes (e.g. reduced/re-distribution of GP/nurse workload, contribution of additional appointments and skillset to the practice).

GOLD=Global Initiative for Chronic Obstructive Lung Disease; HCPs=healthcare practitioners; COPD=chronic obstructive pulmonary disease; mMRC=Modified Medical Research Council; CAT=COPD Assessment Test; LABA=long-acting beta agonist; LAMA=long-acting muscarinic antagonist; ICS=inhaled corticosteroids; QOF=quality and outcomes framework


  1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease 2019 report. GOLD, 2018. Available at:
  2. Brusselle G, Pavord I, Landis S et al. Blood eosinophil levels as a biomarker in COPD. Respir Med 2018; 138: 21–31.
  3. Bafadhel M, Pavord I, Russell R. Eosinophils in COPD: just another biomarker? Lancet Respir Med 2017; 5 (9): 747–759.
  4. Bafadhel M, Peterson S, De Blas M et al. Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomised trials. Lancet Respir Med 2018; 6 (2): 117–126.
  5. Aaron S, Tan W, Bourbeau J et al. Diagnostic instability and reversals of chronic obstructive pulmonary disease diagnosis in individuals with mild to moderate airflow obstruction. Am J Respir Crit Care Med 2017; 196 (3): 306–314.
  6. Schermer T, Robberts B, Crockett A et al. Should the diagnosis of COPD be based on a single spirometry test? NPJ Prim Care Respir Med 2016; 26: 16059.
  7. NICE. Chronic obstructive pulmonary disease in over 16s: diagnosis and management. NICE Guideline 115. NICE, 2018. Available at: