Professor David Halpin describes the key updates in the 2021 GOLD COPD report and highlights new recommendations about patients with COPD and COVID-19

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Professor David Halpin

  • diagnosing and assessing chronic obstructive pulmonary disease (COPD)
  • recent evidence about the role of triple therapy in COPD
  • the impact of COVID-19 on people with COPD.

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In November 2020, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) committee published its 2021 report, Global strategy for the diagnosis, management, and prevention of COPD.1 The report contains recommendations on the diagnosis and assessment of people with chronic obstructive pulmonary disease (COPD), the management of stable disease and exacerbations, and the role of co-morbidities. The 2021 report contains some small but important updates to these recommendations, but the most significant change is the inclusion of a new chapter on COPD and COVID-19.2

In 2018, GOLD held a 1-day summit to consider information about the epidemiology, clinical features, approaches to prevention and control, and the availability of resources for COPD in low and middle income countries (LMICs).3 The GOLD 2021 report begins to take account of the conclusions of the summit by incorporating references to the World Health Organization minimum set of interventions for the diagnosis and management of COPD, but it also highlights that there remains much to be done to improve outcomes in LMICs, including:1

  • there are limited data about the epidemiological and clinical features of COPD in these countries
  • diagnostic spirometry services are not widely available
  • there are major problems with access to affordable quality-assured pharmacological and non-pharmacological therapies.

The 2021 report also emphasises that COPD is still not being taken seriously enough at any level—from individuals and communities to national governments and international agencies—and it is time for this to change.1,4

Diagnosis and assessment of people with COPD

The 2021 GOLD report continues to recommend that a diagnosis of COPD is based on the presence of symptoms and airflow obstruction demonstrated by a postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio of less than 0.7 on spirometry. It states: ‘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)’.1 To achieve these goals, the report recommends that assessment of people with COPD must separately consider the following aspects of the disease:1

  • the presence of the spirometric abnormality and its severity
  • current nature and magnitude of 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 (1–4),1 but the level of symptoms, as determined by the modified MRC breathlessness score (mMRC) or the COPD assessment test (CAT) 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 (see Figure 1).1 The GOLD 2021 report again emphasises that this assessment of symptoms and risk of exacerbations is recommended only as a basis for determining initial therapy and is not designed for reassessing patients during follow up.1

Figure 1 Refined ABCD assessment tool

Figure 1: The refined ABCD assessment tool1

FEV1 =forced expiratory volume in 1 second; FVC=forced vital capacity; GOLD=Global Initiative for Chronic Obstructive Lung Disease; mMRC=modified British Medical Research Council; CAT=COPD assessment test

Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. GOLD, 2021. Available at: www.goldcopd.org

Reproduced with permission

Initial management

Following assessment, initial management should address reducing exposure to risk factors, such as smoking cessation, general advice on healthy living and the patient’s co-morbidities should be provided, and vaccination offered (see Figure 2).1 The GOLD 2021 report now includes the recommendation from the US Centers for Disease Control that tetanus, diphtheria, and pertussis (TdaP) vaccination should be offered to adults with COPD who were not vaccinated in adolescence to protect against pertussis.1

Figure 1 Management of COPD

Figure 2: Management of COPD1

FEV1 =forced expiratory volume in 1 second; GOLD=Global Initiative for Chronic Obstructive Lung Disease; CAT=COPD assessment test; mMRC=modified British Medical Research Council; NIV=non-invasive ventilation

Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. GOLD, 2021. Available at: www.goldcopd.org

Reproduced with permission

Recommendations on pharmacotherapy

The GOLD 2021 report continues to separate recommendations for initial therapy from those on escalation or de-escalation of therapy based on changes in the patient’s breathlessness or exacerbation frequency.

Blood eosinophil counts

The report continues to recommend using the blood eosinophil count as a circulating biomarker to help guide treatment choices to maximise benefit and minimise risk of using inhaled corticosteroid (ICS) therapy. Recent prospective clinical trials have shown that higher blood eosinophil counts are predictive of the efficacy of ICS in reducing exacerbations whereas observational studies show low counts are predictive of an increased risk of developing pneumonia.1 The relationships between the blood eosinophil count and the likelihood of benefit or risk of harm are continuous,1,5,6 but thresholds that can be used as guides in clinical practice are recommended by GOLD.1

Initial pharmacotherapy

Figure 3 shows the recommended initial pharmacotherapy for patients in groups A to D, which is unchanged from the 2020 report.1 Bronchodilators are the recommended initial treatment for patients in groups A, B, and C. The choice of initial therapy for patients in group D who are symptomatic and at risk of exacerbations depends on the intensity of symptoms and may also be influenced by the blood eosinophil count.

Figure 3 Initial pharmacological treatment

Figure 3: Initial pharmacological therapy1

LAMA=long-acting muscarinic antagonist; LABA=long-acting beta2‑agonist; ICS=inhaled corticosteroid; eos=blood eosinophil count in cells per microlitre; mMRC=modified British Medical Research Council; CAT=COPD assessment test

Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. GOLD, 2021. Available at: www.goldcopd.org

Reproduced with permission

Patient review and treatment reassessment

Patients should be reassessed to determine whether the treatment goals of reducing the risk of exacerbations or reducing breathlessness and improving exercise capacity 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 2).1 At this review it is also essential to consider non-pharmacological interventions such as pulmonary rehabilitation and smoking cessation. If the response to the initial therapy is sufficient the treatment should be continued, but if the patient is continuing to have problems despite the initial therapy the treatment should be modified.1

The algorithm proposed by GOLD requires the clinician to identify what the predominant treatable trait is (i.e. persistent dyspnoea, continuing exacerbations, or both) and what therapy the patient is currently receiving (see Figure 4).1 The clinician should then use either the left-hand side of the figure if the problem is persisting dyspnoea or the right-hand side if it is continuing exacerbations either in isolation or with persistent dyspnoea. 

Figure 4 Follow-up pharmacological treatment

Figure 4: Recommended pathways for escalating and de-escalating therapy depending on the current therapy and treatable trait1

LABA=long-acting beta2‑agonist; LAMA=long-acting muscarinic antagonist; ICS=inhaled corticosteroid; eos=blood eosinophil count in cells per microlitre; FEV1 =forced expiratory volume in 1 second

Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. GOLD, 2021. Available at: www.goldcopd.org

Reproduced with permission

Triple therapy

The GOLD 2021 report contains an updated assessment of the benefits of triple therapy with long-acting beta2‑agonist (LABA)/long-acting muscarinic antagonist (LAMA)/ICS based on the results of recent large randomised controlled trials. Triple therapy has been shown to improve lung function, patient reported outcomes and reduce exacerbations when compared with LAMA alone, LABA/LAMA, and LABA/ICS .7–17

Two large 1-year randomised controlled trials—IMPACT (n=10,355) and ETHOS (n=8509)—provide new evidence on mortality reduction with fixed-dose inhaled triple-therapy combinations compared with dual therapy.8,18 Both trials were enriched for symptomatic patients with a history of frequent and/or severe exacerbations and compared a triple therapy (at two ICS dosages in ETHOS) to two dual therapy options (LABA/LAMA and LABA/ICS). Mortality was a pre-specified outcome for the trials, but not a primary endpoint for either study. In IMPACT, mortality in the triple therapy arm was significantly lower compared with the dual bronchodilation arm19 with similar findings observed in ETHOS with the higher dose ICS (but not the lower dose).20 The GOLD 2021 report concludes that these results suggest triple therapy has a beneficial effect on mortality in symptomatic patients with a history of frequent and/or severe exacerbations.1 It also states that further analyses or studies may help determine whether other specific patient subgroups demonstrate a greater survival benefit.1

COPD and COVID-19

The COVID-19 pandemic has led to many challenges for the routine management and diagnosis of COPD, as well as concerns about outcomes for patients.1 The GOLD 2021 report reviews the current evidence about COPD and COVID-19 and makes provisional recommendations based on the current state of knowledge.1 It concludes that, based on current evidence, patients with COPD do not seem to be at greatly increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), possibly reflecting the effect of protective strategies.1 Patients with COPD are at a slightly increased risk of hospitalisation for COVID-19, but the evidence about the risk of developing severe disease and death are contradictory.1 Overall, the magnitude of these risks is lower than might be expected.

The GOLD 2021 report recommends that patients with COPD should follow basic infection control measures to help prevent SARS-CoV-2 infection, including social distancing and washing hands, and whenever possible they should wear masks.1 In most cases, as highlighted in studies about use in the general population, a loose face covering or even a face shield may be tolerable and effective,1,21,22 and wearing a surgical mask does not appear to affect ventilation even in patients with severe airflow limitation.1,23

Many health systems have reduced face-to-face visits during the pandemic and introduced remote consultations using phone and online video calls. A tool is available on the GOLD website to support remote review of COPD patients. The GOLD 2021 report recommends that spirometry should be restricted to urgent or essential situations only, such as prior to interventional procedures or surgery.1 It suggests that when routine spirometry is not available, home measurement of peak expiratory flow (PEF) combined with validated patient questionnaires can be used to support or refute a possible diagnosis of COPD.1 It does, however, point out that PEF does not correlate well with the results of spirometry,24–26 has low specificity,27 and cannot differentiate obstructive and restrictive lung-function abnormalities.1

The use of ICS in the treatment of COPD during the COVID-19 pandemic has been questioned; although it has an overall protective effect against exacerbations in patients with COPD and a history of exacerbations, ICS use is also associated with an increased risk of pneumonia.1 A systematic review identified no clinical studies in patients with COPD concerning the relationship between ICS use and clinical outcomes with coronavirus infections.28 A more recent study suggested ICS use in COPD was not protective against coronavirus infection and raised the possibility that it increased the risk of developing COVID-19,29 but the results are likely to be confounded by the indication for ICS.30 The GOLD 2021 report concludes that there are no conclusive data to support alteration of maintenance COPD pharmacological treatment, including ICS, either to reduce the risk of developing COVID-19, or conversely because of concerns that pharmacological treatment may increase the risk of developing COVID-19 (Figure 5).1

Figure 5 COVID-19 and COPD original

Figure 5: COPD and SARS-CoV-2 infection: clinical features, abnormal investigations, and possible interventions at different stages of the disease2

COPD=chronic obstructive pulmonary disease; SARS-CoV-2=severe acute respiratory syndrome coronavirus 2; ARDS=acute respiratory distress syndrome; SOB=shortness of breath; PaO2=partial pressure of oxygen; FiO2=fraction of inspired oxygen; SIRS=systemic inflammatory response syndrome; VTE=venous thromboembolism; PCR=polymerase chain reaction; CXR=chest radiograph; CT=computed tomography; SpO2=peripheral oxygen saturation; PCT=procalcitonin; CRP=C-reactive protein; LDH=lactate dehydrogenase; IL-6=interleukin-6; BNP=brain natriuretic peptide; PFT=pulmonary function tests; NIV=non-invasive ventilation; HFNT=high-flow nasal therapy; IMV=invasive mechanical ventilation; PR=pulmonary rehabilitation

Reprinted with permission of the American Thoracic Society. Copyright © 2021 American Thoracic Society. All rights reserved. Halpin D, Criner G, Papi A et al. Global Initiative for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease. The 2020 GOLD Science Committee Report on COVID-19 and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2021; 203 (1): 24–36. The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society.

To reduce risks of spreading SARS-CoV-2, many pulmonary rehabilitation programmes have been suspended during the pandemic. The GOLD 2021 report recommends that patients should be encouraged to keep active at home and supported by home-based rehabilitation programmes.1

As highlighted by GOLD, differentiating the symptoms of COVID-19 infection from the usual symptoms of COPD or an exacerbation can be challenging: ‘Cough and breathlessness are found in over 60% of patients with COVID-19, but are usually also accompanied by fever (>60% of patients) as well as fatigue, confusion, diarrhoea, nausea, vomiting, muscle aches and pains, anosmia, dysgeusia, and headaches.’1 These additional symptoms may suggest a diagnosis of COVID-1931 and testing for SARS-CoV-2 should be considered. Detection of SARS-CoV-2 does not exclude the potential for co-infection with other respiratory pathogens and testing for other causes of respiratory illness is also recommended.32

Chest radiography is indicated in patients with COPD with moderate to severe symptoms of COVID-19,1 with mostly bilateral changes seen with COVID-19 pneumonia.1,33 Alternative diagnoses, such as lobar pneumonia, pneumothorax, or pleural effusion, can also be excluded or confirmed with chest radiography. Patients with COVID-19 are at increased risk of venous thromboembolism34–37 and computed tomography pulmonary angiography should be performed if pulmonary embolism is suspected.1

Systemic steroids and antibiotics should be used in COPD exacerbations according to the usual indications.1 Patients with COPD who are hospitalised with moderate to severe COVID-19 and pneumonia should be treated with the evolving pharmacotherapeutic approaches, as appropriate, such as dexamethasone and anticoagulation to prevent venous thromboembolism.1 Management of acute respiratory failure should include appropriate oxygen supplementation, prone positioning, high-flow nasal oxygen, non-invasive ventilation, and invasive mechanical ventilation if indicated.1

The report recommends that rehabilitation should be provided to all COPD patients recovering from COVID-19. Patients who develop mild COVID-19 should be followed up as usual, but those with moderate or severe COVID-19 should be monitored more frequently, particularly with regard to their need for oxygen therapy.1

Summary

The GOLD 2021 report does not make any major changes to the recommendations for the diagnosis and assessment of COPD nor for the management of stable disease or exacerbations. The new chapter on COPD and COVID-19 recommends that there is no need to change the pharmacological and non-pharmacological management of stable COPD, but if patients have symptoms of an exacerbation or suggestive of COVID-19 they should be tested for SARS-CoV-2 infection and managed accordingly.

Professor David Halpin

Consultant Physician and Honorary Professor of Respiratory Medicine, University of Exeter Medical School

Member of the GOLD Board of Directors and Science Committee

Key points

  • There were no significant changes to the recommendations on management of COPD, including pharmacotherapy, in the 2021 update to the GOLD report
  • Multidimensional assessment of COPD based on spirometry, symptoms, exacerbation risk, and presence of co-morbidities remains essential
  • There is a new recommendation that the TdaP vaccination should be offered to patients with COPD who were not vaccinated in adolescence to protect against pertussis
  • 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. 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 with the new therapy being determined by both what their current therapy is and the trait requiring treatment
  • Long-acting bronchodilators remain the mainstay of pharmacotherapy
  • It is recommended that the use of ICS is guided by the blood eosinophil count
  • The pharmacological and non-pharmacological management of stable COPD does not need to change during the coronavirus pandemic
  • If patients have symptoms of an exacerbation or COVID-19 they should be tested for SARS-CoV-2 infection and managed accordingly.

COPD=chronic obstructive pulmonary disease; GOLD=Global Initiative for Chronic Obstructive Lung Disease; TdaP=tetanus, diphtheria, and pertussis; ICS=inhaled corticosteroid; SARS-CoV-2=severe acute respiratory syndrome coronavirus 2

Implementation actions for STPs and ICSs

written by Dr David Jenner, GP, Cullompton, Devon

The following implementation actions are designed to support STPs and ICSs with the challenges involved with implementing new guidance at a system level. Our aim is to help you consider how to deliver improvements to healthcare within the available resources.

  • Share this strategy widely among primary and secondary care teams, including out-of-hours providers
  • Consider publishing a summary sheet of the recommendations for local management of COPD during the COVID-19 pandemic, including diagnosis without access to spirometry
  • Encourage the use of blood eosinophil levels to guide use of inhaled corticosteroids
  • Investigate the feasibility of offering TdaP vaccination to those with no history of childhood vaccination and offering incentives to GP practices to provide this
  • Reassure practices and patients that no change to the use of inhaled and systemic steroids for COPD and its exacerbations is advised during the COVID-19 pandemic.

STP=sustainability and transformation partnership; ICS=integrated care system; COPD=chronic obstructive pulmonary disease; TdaP=tetanus, diptheria, and pertussis

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After reading this article, ‘Test and reflect’ on your updated knowledge with our multiple-choice questions. We estimate that this activity will take you 30 minutes—worth 0.5 CPD credits.

References

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