CHEST Investigations Explore COPD Guideline Adherence, Adding Ensifentrine, and Use of AI in Education

The quality of treatment patients with chronic obstructive pulmonary disease (COPD) receive in real-world settings—and how that affects long-term outcomes—was the umbrella for a series of investigations on the opening day of CHEST: the American College of Chest Physicians Annual Meeting, taking place in Phoenix, Arizona. Sunday’s session, “Reframing COPD: Phenotypes, Outcomes, Therapeutics, and the Future of Care Delivery,” featured studies based on real-world evidence.

Approximately 11.1 million people in the US are diagnosed with COPD, and up to 25 million are living with lung function consistent with COPD. The disease accounts for 1.5 millionvisits to the emergency department (ED) each year, contributing health costs of $50 billion annually, according to a study cited by the American Lung Association.¹

Presentations from the session included the following:

Most Patients Are Discharged on Inhalers That Don’t Follow Guidelines

Most patients hospitalized for COPD exacerbations at a tertiary care center left the hospital on inhaler regimens that did not follow guidelines, according to a study presented at the session.² Every patient readmitted within 30 days had been discharged on such a regimen, according to research presented by Chineen Shah, MBBS, pulmonary and critical care medicine fellow at Geisinger Medical Center in Danville, Pennsylvania.

Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines call for dual bronchodilation with a long-acting beta agonist (LABA) and a long-acting muscarinic antagonist (LAMA) when exacerbations recur or lead to hospitalization. As the investigators noted in their abstract, inhaled corticosteroids (ICS) are to be reserved for patients with eosinophilia or coexisting asthma.

Shah and colleagues reviewed charts from 199 hospital encounters involving 145 patients admitted in 2023 and 2024. The patients’ mean age was 70 years; 54% were male, 45% were White, and 41% were Black.

At discharge, 79% of patients were prescribed a LABA, with 36% receiving a LAMA; 32% received both. ICS were prescribed to 78% of patients, and 53% received ICS without eosinophilia or asthma.

“Overall, only 10% of patients were discharged on inhaler regimens fully consistent with recommendations,” they wrote.

There were no demographic or clinical differences between patients who did and did not receive guideline-adherent therapy. All 11 patients readmitted within 30 days had been discharged on regimens that did not follow guidelines. Of those 11, 91% received ICS, most without a clear indication.

“Our study highlights a significant disconnect between evidence-based COPD management and real-world prescribing patterns at hospital discharge,” the authors wrote. “Inappropriate use of ICS and under-utilization of recommended bronchodilators are widespread.”

Because prescribing did not vary across patient groups, the authors concluded that the problem “lies not in patient complexity, but in clinical practice patterns.” They called for institutional efforts, including education and clinical decision support tools, to promote guideline-adherent care. These quality improvement steps, they wrote, could reduce readmissions and ensure patients go home on the most effective and safest regimens.

Adding Ensifentrine to Triple Therapy Linked to Fewer Hospital Visits, Deaths

Adding ensifentrine to inhaled triple therapy was associated with fewer respiratory complications, emergency visits, cardiovascular events, and deaths among patients COPD, according to a real-world analysis presented at CHEST 2026.³

Ensifentrine (Ohtuvayre; Verona/Merck) is a first-in-class dual phosphodiesterase-3/4 inhibitor approved in 2024 that works both as a bronchodilator and an anti-inflammatory. It reduced exacerbations in the phase 3 ENHANCE-1 and ENHANCE-2 trials.⁴ However, as the investigators noted, “only a minority of enrolled patients were receiving maximized inhaled triple therapy or had substantial prior exacerbation history.”

Navneet Gupta, MD, an internal medicine resident at Allegheny Health Network, and colleagues used the TriNetX US Collaborative Network for the analysis. They compared adults with COPD taking ensifentrine plus triple therapy (LABA/LAMA/ICS) with those on triple therapy alone. Before matching, the ensifentrine group was much sicker: 54% had an exacerbation in the prior year vs 9.5% of controls, and 37% used oxygen vs 7%. After propensity score matching, each group had 1429 patients.

Compared with triple therapy alone, adding ensifentrine was associated with improved odds on multiple outcomes measures (See Table). The need for new supplemental oxygen did not increase.

“These real-world data support integration of ensifentrine as an effective add-on therapy for patients with moderate-to-severe or refractory COPD,” the authors wrote.

The presentation noted 2 limitations: confounding may remain despite propensity score matching, and the researchers could not confirm whether patients took their medications as prescribed.

Cancer and Stroke Deaths Rise Among Veterans With COPD

Veterans with COPD are dying less often from respiratory and ischemic heart disease than they did 25 years ago, but deaths from cancer and stroke are inching upward, according to research presented Sunday at CHEST 2026, the annual meeting of the American College of Chest Physicians.⁵

Amir Sharafkhaneh, MD, PhD, professor of medicine, medical director of AI in Health, Baylor College of Medicine, presented the retrospective analysis of Veterans Affairs (VA) data. The investigators noted that survival in COPD has improved, but how causes of death have shifted over time remains poorly understood.

The cohort included 2,459,339 veterans with confirmed COPD and no asthma diagnosis (mean age, 67 years; 96% male; 69% White). During a median follow-up of 8.3 years (±6.1 years), the data show 1,653,000 (67%) died. Malignant neoplasms were the leading cause of death (16.1%), followed by ischemic heart disease (14.1%), chronic lower respiratory diseases (13.3%), and cerebrovascular disease (3.1%).

The researchers tracked trends across 5 eras, from 2000-2004 through 2020-2026. They adjusted for age, sex, race/ethnicity, comorbidity burden, body mass index, and smoking status. With each 5-year era, the adjusted odds of death fell 5% for chronic lower respiratory disease (adjusted OR [aOR], 0.95; 95% CI, 0.94-0.95) and for ischemic heart disease (aOR, 0.94; 95% CI, 0.94-0.95). Malignancy-related deaths rose 3% per era (aOR, 1.03; 95% CI, 1.03-1.04), and cerebrovascular deaths rose 2% (aOR, 1.02; 95% CI, 1.01-1.03); all P < .001.

“The shift from respiratory-centric mortality to increased malignancy and cerebrovascular-related deaths suggests that COPD management must evolve beyond lung function alone,” the authors wrote in their abstract. They urged clinicians to prioritize “integrated multimorbidity screening, particularly aggressive lung cancer surveillance and stroke prevention.”

The investigators said future research should find out what drove the declines in respiratory and cardiovascular deaths. Possible factors include medications, vaccinations, changes in care delivery, guideline implementation, and earlier diagnosis.

GPT-4 Outscores Newer AI Tools for COPD Patient Education

When pulmonologists blindly graded COPD patient education written by 4 artificial intelligence (AI) tools, an older general-purpose model, GPT-4, came out on top. A medical literature tool produced the fewest safety flags but less complete answers, according to research presented at CHEST 2026.⁶

Patient education shapes inhaler technique, medication adherence, and how quickly patients recognize exacerbations. Large language models are increasingly used to write patient-facing content but are rarely benchmarked against GOLD guidelines, said Rachana Phadke, MD, of Internal Medicine at Saint Vincent Hospital in Worcester, Massachusetts.

The investigators wrote standardized prompts from the 2025 GOLD Pocket Guide across 9 domains, ranging from disease overview and inhaler technique to exacerbation action plans and cost. GPT-4, GPT-5, Gemini, and OpenEvidence each generated 3 responses per question. With model names removed, 2 board-certified pulmonologists scored the responses on 6 measures: adequacy and comprehensiveness, readability, empathy, understandability and actionability, safety, and GOLD concordance.

GPT-4 had the highest composite performance and top median scores for adequacy, comprehensiveness, empathy, and guideline concordance. It also met the 8th-grade readability target most consistently. GPT-5 ranked a close second, and the differences between the 2 models were not statistically significant. Gemini and OpenEvidence scored significantly lower than GPT-4 on adequacy, comprehensiveness, and guideline adherence, with weaker guideline specificity and exacerbation safety instructions.

Safety concerns and hallucinations were infrequent overall and lowest with OpenEvidence. But as Phadke’s presentation put it, “safe is not the same as adequate,” and “newer is not necessarily better.”

“Meaningful differences in accuracy, guideline alignment, and safety across models highlight the need for structured, expert-driven validation before clinical integration,” the authors wrote in their abstract.

Limitations included rapidly evolving models, a fixed set of prompts, and reliance on 2 expert raters rather than patient outcomes. Next steps include testing whether patients understand the material, studies linked to outcomes, and repeating the benchmarking regularly.

References

1. COPD in your state. American Lung Association. Updated September 2, 2025. Accessed October 18, 2026. https://www.lung.org/lung-health-diseases/lung-disease-lookup/copd/for-health-professionals/copd-in-your-state

2. Shah C, Miele A, Martinez CE, et al. Review of inhaler prescribing patterns at hospital discharge following COPD exacerbations. Chest. 2026;170(suppl 4):abstr 7.3935. doi:10.1016/j.chest.2026.07.3935

3. Gupta N, Le Aishwarya JP, Zayaan M, et al. Real-world effectiveness of adjunctive ensifentrine in COPD patients receiving inhaled triple therapy: a propensity-matched US cohort study. Chest. 2026;170(Suppl 4):abstr doi:10.1016/j.chest.2026.07.3937

4. Anzueto A, Barjaktarevic IZ, Siler TM, et al. Ensifentrine, a novel phosphodiesterase 3 and 4 inhibitor for the treatment of chronic obstructive pulmonary disease: randomized, double-blind, placebo-controlled, multicenter phase III Trials (the ENHANCE Trials). Am J Respir Crit Care Med. 2023;208(4):406-416. doi:10.1164/rccm.202306-0944OC

5. Razjouyan J, Aminnia S, Hanania NA, Sharafkhaneh A. Changing patterns of mortality in COPD: A 25-year analysis of Veterans Affairs data. Chest. 2026;170(suppl 4):abstr 7.3899. doi:10.1016/j.chest.2026.07.3899

6. Phadke R, Singh A, Thirupathay U, O’Shea Paudel E. Benchmarking artificial intelligence for COPD patient education: A blinded comparative evaluation of GPT-4, GPT-5, Gemini, and OpenEvidence. Chest.2026;170(supp 4):abstr 7.3936. doi:10.1016/j.chest.2026.07.3936