The 2023 report from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) — “Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease” (COPD)1 — details “an expanded range of therapies for COPD that now can be considered to improve mortality,” according to Gerard J. Criner, MD, FACP, FACCP, an author of the 2023 GOLD Report and director of the 2022 GOLD COPD Day conference, held in November, where the updated 5th version of the GOLD report was released and the scientific underpinnings of the updates were discussed.
The expanded range of COPD therapies discussed in the 2023 report includes “an expanded role of triple inhaled therapy in select patient populations, as well as noninvasive ventilation, which also may have a role in improving exacerbation in select patient groups with COPD,” said Dr Criner, who is Chair and Professor of Thoracic Medicine and Surgery at the Lewis Katz School of Medicine at Temple University in Philadelphia, which hosts the annual GOLD COPD Day conference.
The 2023 GOLD report contains numerous other important updates as well. Among these are a reconsideration of the definitions and taxonomy of COPD and symptomatic exacerbations; new material on chronic bronchitis; and an increased focus on genetic and environmental causal factors in COPD aside from tobacco smoking.
Definitions, Heterogeneity, and Exacerbations
An important change in the 2023 GOLD report involves “clarifications and suggestions on the definition of COPD,” said Dr Criner. Related to this, the updated report also has expanded the discussion of how an exacerbation is defined, he added. “We’ve integrated newer work on codifying the onset of an exacerbation and defining the severity of an exacerbation by using not only symptoms but also physiologic criteria in grading the exacerbation as mild, moderate, or severe. Now that’s more a hypothesis than something with data wrapped around it, but is meant to fuel thought into how we can do a better job of assessing exacerbations.”
The revised definition of COPD in the 2023 report “now describes symptoms clearly and underscores the heterogeneity of COPD,” said Fernando J. Martinez, MD, MS, another coauthor of the 2023 GOLD Report. “GOLD has now embraced the concept of both early COPD and pre-COPD, and this now is incorporated into the GOLD document,” explained Dr Martinez, who is also Chief of the Pulmonary and Critical Care Medicine Division at Weill Cornell Medicine in New York City.
“There’s a lot of interest right now regarding the heterogeneity of COPD,” added Dr Martinez. “Two very relevant articles recently advocated for highlighting that heterogeneity in the definition of COPD.2,3 Exactly what implication that’s going to have for patient management and therapeutics, no one yet knows. But that level of heterogeneity is now something that’s very clearly seen as an important component of COPD in general,” he stressed.
With regard to defining exacerbations and their severity, Dr Martinez added, “the science committee recommended adopting the ’Rome Proposal,4 which suggested that the definition of severity should evolve away from what therapies are used, and rather toward a series of objective parameters: how bad the symptoms are, whether there’s evidence of inflammation or an oxygen saturation problem, and so on. So that is a recommendation that was made for consideration only at this time, because it is not yet clear whether it has any therapeutic implications,” said Dr Martinez.
Assessment Schema and Pharmacotherapy
The evolution of GOLD’s approach to pharmacotherapeutic assessment for COPD — one of the topics “of greatest interest” at the 2022 COPD Day conference, according to Dr Martinez — is covered at length in the 2023 GOLD report.
Until the release of the 2023 report, it was recommended that clinicians determine a patient’s initial COPD pharmacologic regimen using the “ABCD Assessment Tool,” said Dr Criner, who described the tool as “a sort of ‘four squared’ algorithm…based on symptoms and exacerbation history.” First presented in the 2011 GOLD report and later refined in the 2017 GOLD report, the ABCD Assessment Tool was “based on the patient’s level of symptoms, future risk of exacerbations, the extent of airflow limitation, the spirometric abnormality, and the identification of comorbidities” and was “a major advance from the simple spirometric grading system” used previously, the 2018 GOLD report stated.5
Based on recent evidence, however, the 2023 GOLD report has further revised this tool, which is now called the “ABE Assessment Tool.”1 According to the 2023 report, this change recognizes the clinical relevance of exacerbations, independent of the level of symptoms, in making assessments. As Dr Martinez explains it, “This year we got rid of the ‘C’ [ie, less symptomatic, high-exacerbation-risk] and ‘D’ [ie, more symptomatic, high-risk] groups in the ABCD tool, and merged them into one ‘E’ group, representing exacerbation-prone patients. This was partly because the ‘C’ group was so uncommon in large population studies, and partly because the exacerbation component is such a crucial issue to address.”
The 2023 GOLD report also included significant changes in COPD pharmacotherapeutic strategy, said Dr Martinez. The first change is in line with the American Thoracic Society/European Respiratory Society (ATS/ERS) statement that combination bronchodilator therapy — a long-acting beta agonist (LABA) and a long-acting muscarinic antagonist (LAMA) together — is better than LABA or LAMA as monotherapy,6,7 he explained. “We now recommend dual bronchodilator therapy up front for symptomatic patients. There was advocacy for this for many years, and we finally made that change.”
“There is increasing awareness that dual bronchodilator therapy is initially indicated in people who are symptomatic or have exacerbations,” said Dr Criner. “This includes people who have COPD exacerbations and have peripheral blood eosinophilia.”
Yet more discussion on this topic seems inevitable; as Dr Martinez noted, “implementation of dual bronchodilator therapy and quantitative cutoff values for eosinophilia in treatment selection” were the subject of “spirited debates,” at the recent COPD Day Conference.
Another significant change in COPD pharmacotherapeutic strategy in the 2023 GOLD report is the recommendation to use inhaled triple therapy rather than inhaled corticosteroid (ICS)-plus-LABA for higher-risk patients who are more symptomatic and exacerbation prone. After much debate, the GOLD science committee concluded that for these patients, “triple therapy beats ICS/LABA in every category,” said Dr Martinez, who was involved with 2 or 3 major studies of these therapies. 8,9 As a result, said Dr Martinez, “ICS/LABA has been dropped from the therapeutic recommendations in GOLD. That is a major change. ICS/LABA remains one of those commonly used regimens globally. There are various generic formulations, and payers love it, because it’s cheap; but now it’s dropped off the GOLD therapeutic strategy. So it will be interesting to see how payers interpret that.”
To support this change, the 2023 report highlights “very convincing data that triple therapy, in a particular population of patients, can improve all-cause mortality.10,11 We included a tabular representation of all of the studies that have shown improvements in mortality, for pharmacotherapy and nonpharmacotherapy, and we recommend that be incorporated into therapeutic decision-making for individual patients,” Dr Martinez noted. “So the management recommendations for stable COPD have now changed to emphasize dual bronchodilators and triple therapy, and also with a strong emphasis on the eosinophil as a circulating biomarker that can be used to guide response.”
Chronic Bronchitis and Mucus Hypersecretion
The burden of mucus hypersecretion in patients with COPD is also covered in the 2023 report, said Dr Criner. In particular, chronic bronchitis is discussed at greater length, with a review of some of its pathobiology and epidemiology, as well as a discussion of new medical and interventional treatments.
“There is a lot of interest in particular symptoms such as cough and sputum production. But it’s only recently that the clinical implications of those symptoms have become evident,” said Dr Martinez. He added that “the effort to target a particular symptomatic expression of COPD, such as cough and sputum production, is now a very active area, with practical implications for patients. Interventional studies are ongoing; and oral pharmacotherapeutic approaches, including cystic fibrosis transmembrane conductance regulator (CFTR) potentiators,12 are under evaluation right now.”
Vascular Disease and Other Updates
The 2023 report also discusses pulmonary vascular diseases, both secondary pulmonary hypertension and pulmonary embolism. The latter has been the focus of more recent studies, including a large French study published in JAMA.13 As Dr Criner explained, “In that study, about 6% of patients who presented with an acute exacerbation of COPD were found to have a pulmonary embolism at the time of presentation.” This study “highlights the fact that some people with COPD exacerbations actually have COPD with exacerbation of symptoms that are due to another cause, such as pulmonary embolism, heart failure, or ischemic heart disease” — a topic of interest that was discussed during the conference, said Dr Criner. Accordingly, he noted, the importance of screening patients with COPD for comorbid conditions like pulmonary embolism and other diseases is reflected in the 2023 GOLD report.
Certain sections of the new report have some degree of updated information but were not exhaustively revised, said Dr Criner. “We discuss imaging more than previously, particularly the role of computed tomography (CT) scanning — both its current role and the role we think it will have in the future. We have also expanded and revised the discussion of surgical and interventional treatments for COPD. This includes indications for bullectomy or lung reduction surgery; bronchoscopic treatments for lung reduction, an evolving field both in and outside the US; and interventional treatments that are currently being studied for chronic bronchitis. There is also a more comprehensive discussion of the role, benefits, and complications of lung transplantation. Finally, we revised and updated chapters on comorbidities and on COVID-19.”
Interstitial Lung Abnormalities: A Future Topic
Interstitial lung abnormalities in patients with COPD was a topic of interest at the GOLD conference that was not exhaustively covered in the 2023 GOLD report, said Dr Criner. Interstitial lung abnormalities “have been reported in several epidemiologic studies, mainly imaging studies characterizing patients who have been exposed to smoke, and also studies of lung cancer screening data. These studies demonstrate that patients with COPD have some interstitial changes that could be related to smoke exposure, or occupational exposure, or smoking in people who also are predisposed to interstitial lung diseases,” said Dr Criner. This topic is likely to be a focus in the future, he added.
Disclosures:Dr Criner reports receiving grants from AstraZeneca, Boehringer Ingelheim, Broncus, Chiesi, Corvus, Genentech, Gilead, GlaxoSmithKline, Fisher-Paykel Healthcare, Lilly, NIH-NHLBI, Novartis, Olympus, PA-DOH, Pfizer, Pearl, PneumRx, Pulmonx, Regeneron, Roche and Spiration; consultant fees from Almirall, AstraZeneca, Broncus, BTG, CSA Medical, GlaxoSmithKline, EOLO, Intuitive, Ion, Mereo, Nuvaira, PneumRx, Pulmonx, Regeneron and Sanofi; and an equity interest in Free Flow Medical and Pleural Dynamics. Dr Martinez reports receiving fees for consulting and/or speaker roles with AstraZeneca, Boehringer Ingelheim, Chiesi, Sanofi/Regeneron, CSL, Behring, GlaxoSmithKline, Medtronic, Novartis, Polarean, Pulmatrix, Pulmonx, and Theravance/Viatris.
- Vogelmeier CF, Criner GJ, Martinez FJ, et al; GOLD Scientific Committee. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis Management, and Prevention of Chronic Obstructive Pulmonary Disease 2023 Report. Accessed January 18, 2023.
- Celli B, Fabbri L, Criner G, et al. Definition and nomenclature of chronic obstructive pulmonary disease: time for its revision. Am J Respir Crit Care Med. 2022;206(11):1317-1325. doi:10.1164/rccm.202204-0671PP
- Stolz D, Mkorombindo T, Schumann DM, et al. Towards the elimination of chronic obstructive pulmonary disease: a Lancet Commission. The Lancet. 2022;400(10356):921-972. doi:10.1016/S0140-6736(22)01273-9
- Celli BR, Fabbri LM, Aaron SD, et al. An updated definition and severity classification of chronic obstructive pulmonary disease exacerbations: the Rome proposal. Am J Respir Crit Care Med. 2021;204(11):1251-1258. doi:10.1164/rccm.202108-1819PP
- Vogelmeier CF, Criner GJ, Martinez FJ, et al; GOLD Scientific Committee. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2018 Report. Accessed January 18. 2023.
- Nici L, Mammen MJ, Charbek E, et al. Pharmacologic management of chronic obstructive pulmonary disease. An official American thoracic society clinical practice guideline. Am J Respir Crit Care Med. 2020;201(9):e56-e69. doi:10.1164/rccm.202003-0625ST
- Mammen MJ, Pai V, Aaron SD, Nici L, Alhazzani W, Alexander PE. Dual LABA/LAMA therapy versus LABA or LAMA monotherapy for chronic obstructive pulmonary disease. A systematic review and meta-analysis in support of the American thoracic society clinical practice guideline. Ann Am Thorac Soc. 2020;17(9):1133-1143. doi:10.1513/AnnalsATS.201912-915OC
- Lipson DA, Barnhart F, Brealey N, et al. Once-daily single-inhaler triple versus dual therapy in patients with COPD. N Engl J Med. 2018;378(18):1671-1680. doi:10.1056/NEJMoa1713901
- Frith PA, Thompson PJ, Ratnavadivel R, et al. Glycopyrronium once-daily significantly improves lung function and health status when combined with salmeterol/fluticasone in patients with COPD: the GLISTEN study—a randomised controlled trial. Thorax. 2015;70(6):519-527. doi:10.1136/thoraxjnl-2014-206670
- Lipson DA, Crim C, Criner GJ, et al. Reduction in all-cause mortality with fluticasone furoate/umeclidinium/vilanterol in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2020;201(12):1508-1516. doi:10.1164/rccm.201911-2207OC
- Rabe KF, Martinez FJ, Ferguson GT, et al. Triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD. N Engl J Med. 2020;383(1):35-48. doi:10.1056/NEJMoa1916046
- Rowe SM, Jones I, Dransfield MT, et al. Efficacy and safety of the CFTR potentiator icenticaftor (QBW251) in COPD: results from a phase 2 randomized trial. Int J Chron Obstruct Pulmon Dis. 2020;15:2399-2409. doi:10.2147/COPD.S257474
- Couturaud F, Bertoletti L, Pastre J, et al. Prevalence of pulmonary embolism among patients With COPD hospitalized with acutely worsening respiratory symptoms. JAMA. 2021;325(1):59-68. doi:10.1001/jama.2020.23567