2025 GOLD report addresses cardiovascular risk, climate change, pulmonary hypertension

Key takeaways:

• The 2025 GOLD report newly highlights cardiovascular risk, climate change and pulmonary hypertension in the context of COPD.
• Updates have been made to sections on spirometry and pharmacological treatments.

PHILADELPHIA — To reflect developments in COPD research and care, the 2025 Global Initiative for Chronic Obstructive Lung Disease report features three new sections and several sections that have been updated/revised.

Claus F. Vogelmeier, MD, chair of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) science committee and professor at Philipps University of Marburg, presented key changes of the report during the 2024 GOLD COPD conference.

Last year, Healio reported on key changes in the 2024 report.

New sections

The 2025 report contains three new sections on cardiovascular risk, climate change and pulmonary hypertension.

“We now consider cardiovascular risk to be one of the major drivers of COPD ... therefore we added a major paragraph in this regard,” Vogelmeier said.

During his discussion on the cardiovascular risk section, Vogelmeier noted that cardiovascular diseases impact all patients with COPD, even those classified as clinically stable.

He also emphasized that experiences of exacerbations contribute to an elevated cardiovascular risk, which are possibly due to three different mechanisms.

“The idea is that inflammation may play a role,” Vogelmeier said. “Hyperinflation may [also] play a role by compressing vessels in the lung, and in particular during exacerbations, it also may be driven by hypoxemia.”

As Healio previously reported, the EXACOS-CV US study found that patients who experienced a COPD exacerbation had a greater risk for acute cardiovascular events than patients who did not.

Further, Vogelmeier presented data from another EXACOS-CV study that reported a heightened risk for a severe CV event or all-cause mortality up to 12 months after a severe exacerbation.

“Right now, we have in the document some suggestions what you should do in the weeks after exacerbation,” Vogelmeier said. “So, 1 to 4 weeks follow-up [and] 12 to 16 weeks follow-up, we say determine status of comorbidities.

“I believe that this is not good enough, that we have to move on in that direction to give more specific recommendations, what you have to do regarding diagnosis and treatment, but this is for the years to come,” he added.

The second new section focuses on climate change and COPD.

“One part of this chapter is about heat and cold,” Vogelmeier said. “We learned that higher outdoor temperatures are associated with an increased risk of hospitalization for COPD, and that low outdoor temperatures are associated with increased risk of exacerbations.”

As Healio previously reported, extreme heat is just one result of climate change that leads to negative outcomes for patients with lung diseases, with the most serious outcome being death.

Notably, a study published in American Journal of Respiratory and Critical Care Medicine found that exposure to both extreme heat and air pollution were linked to an increased risk for all-cause mortality.

The last new section is dedicated to pulmonary hypertension, which Vogelmeier said “has been underestimated as yet.”

Within this chapter, there is a figure that breaks down how clinicians should manage patients with pulmonary hypertension-COPD based on their pulmonary hypertension group.

During his presentation, Vogelmeier said the 2022 ESC/ERS pulmonary hypertension guidelines should be used when treating patients with COPD and PAH (group 1), as well as when treating patients with COPD and chronic thromboembolic pulmonary hypertension (group 4). However, the suggested management is different for patients with COPD and severe pulmonary hypertension associated with lung diseases and/or hypoxia (group 3).

“[In group 3 pulmonary hypertension,] you need an individual treatment approach, and they should be referred to a center that knows more about this problem,” Vogelmeier said.

Updated sections

In addition to the various new sections added, several sections have been updated or revised to reflect current evidence on the topic.

To address the presence of several competing options for the best reference standard for spirometry, the section on spirometry in GOLD 2025 now features information on lower limit of normal vs. fixed FEV₁/FVC ratio, z scores and reference values.

According to Vogelmeier and stated in the 2025 report, fixed ratio is preferred over lower limit of normal for defining airflow obstruction, but there is a possibility of overdiagnosis in older adults when using the fixed ratio.

To diagnose an individual with COPD, a post-bronchodilator FEV₁/FVC less than 0.7 is required, according to Vogelmeier’s presentation.

“You have to have symptoms and risk factors to start with, and only sort of this combination of these symptoms and risk factors then drives you to perform a spirometry,” Vogelmeier said.

During the discussion on lung function reference values, specifically on the use of race-neutral vs. race-specific equations, Vogelmeier showed results from a New England Journal of Medicine study presented at the 2024 American Thoracic Society International Conference. As Healio previously reported, millions of individuals had different clinical, occupational and financial outcomes with race-neutral (Global Lung Function Initiative [GLI]-Global) vs. race-specific (GLI-2012) lung function equations, and outcomes often changed to a greater degree among Black patients compared with white patients and Hispanic patients.

“Based on all of what we know right now, we think that the GLI-Global equations should be used as a reference standard for the assessment of lung function impairment,” Vogelmeier said.

The 2025 report also features a new graph demonstrating that clinicians should measure post-bronchodilator FEV₁/FVC if the pre-bronchodilator ratio is less than 0.7. If the post-bronchodilator value is also less than 0.7, then COPD is confirmed, according to Vogelmeier and the figure in the report.

“If the [pre-bronchodilator] FEV₁/FVC ratio is at least 0.7, then there is no argument for making the diagnosis of COPD, except there is the idea that this patient may be a so-called volume responder,” Vogelmeier said.

“This could be suspected if the FEV₁ is low or if the individual has high symptoms,” he added.

Another 2025 report update that provides more information on a topic takes place in the CT paragraph, which now addresses use of CT for detecting/defining emphysema, lung nodules, airways and COPD-related morbidities, according to Vogelmeier.

Importantly, both ensifentrine (Ohtuvayre, Verona Pharma) and dupilumab (Dupixent; Regeneron, Sanofi) received FDA approval for treating COPD this year, so the new GOLD report details when they should be used.

As Healio previously reported, the FDA based its decision on Ohtuvayre, in part, on data from the global, multicenter, randomized, double blind, parallel-group, placebo-controlled phase 3 ENHANCE trials, which found that 3 mg of twice-daily Ohtuvayre improved measures of lung function, quality of life and exacerbation rate over 12 or 24 weeks in adults with moderate to severe COPD.

Under the “Follow-up Pharmacological Treatment” figure, Vogelmeier said “consider adding ensifentrine when patients on LABA plus LAMA still have considerable symptoms” is now listed.

For dupilumab, the FDA’s decision was, in part, based on findings from the multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 3 BOREAS and NOTUS studies, according to a manufacturer-issued press release. Both studies included patients primarily on triple therapy.

A pooled analysis of these two trials presented at this year’s European Respiratory Society International Congress showed that 300 mg dupilumab every 2 weeks led to improvement in annualized exacerbation rate and pre-bronchodilator FEV₁ in current/former smokers with moderate to severe COPD and type 2 inflammation (blood eosinophil count 300 cells/μL) at week 52.

“We say in the document that in patients with moderate to severe COPD with a history of exacerbations, chronic bronchitis and higher blood eosinophil counts of at least 300 cells/μL, dupilumab reduces exacerbations, improves lung function and quality of life,” Vogelmeier said.

Additionally, Vogelmeier reported that dupilumab is now listed in the “Follow-up Pharmacological Treatment” figure as an option “if patients on LABA plus LAMA plus ICS still have exacerbations” and meet the eosinophil count noted above.

The last major revision made in the 2025 GOLD report happened in the withdrawal of ICS section.

To accompany this change, Vogelmeier highlighted that there is a new graph in the report titled “Management of Patients Currently on LABA + ICS” that breaks down these patients into those with current exacerbations, no relevant exacerbation history and no current exacerbations plus previous positive treatment response to help clinicians make treatment decisions.

“We do not recommend the use of LABA plus ICS any longer for treating patient with COPD because it's very clear that if there is an indication for ICS, triple is superior to LABA plus ICS,” Vogelmeier said.

References:

• Global initiative for chronic obstructive lung disease 2025 report. https://goldcopd.org/wp-content/uploads/2024/11/GOLD-2025-Report-v1.0-12Nov2024_WMV-Draft.pdf. Accessed Nov. 13, 2024.
• Global Initiative for chronic obstructive lung disease 2025 pocket guide. https://goldcopd.org/wp-content/uploads/2024/11/Pocket-Guide-2025-v1.0-12Nov2024_WMV-Draft.pdf. Accessed Nov. 13, 2024.
• GOLD report 2025 key changes summary. https://goldcopd.org/wp-content/uploads/2024/11/KEY-CHANGES-GOLD-2025-11Nov2024.pdf. Accessed Nov. 13, 2024.
• Press release: Dupixent approved in the US as the first-ever biologic medicine for patients with COPD. https://www.sanofi.com/en/media-room/press-releases/2024/2024-09-27-13-35-00-2954551. Published Sept. 27, 2024. Accessed Sept. 27, 2024.
• Rahman MM, et al. Am J Respir Crit Care Med. 2022;doi:10.1164/rccm.202204-0657OC.