The Clinical Year in Review series at the ATS 2025 International Conference concluded on Wednesday, May 21, with a discussion of impactful studies spanning pulmonary vascular disease, chronic obstructive pulmonary disease (COPD), pulmonary rehabilitation, and lung cancer.

Pulmonary Vascular Disease

Roberto Bernardo, MD, MS, ATSF, assistant professor of medicine and director of the pulmonary hypertension program at Indiana University School of Medicine, summarized what he described as “some of the most meaningful articles in pulmonary vascular disease.”

Dr. Bernardo discussed the Torrey study of inhaled seralutinib in patients receiving background therapy for pulmonary arterial hypertension (PAH). Based on the improved pulmonary vascular resistance with seralutinib, especially in patients with intermediate/high risk of mortality (REVEAL 2.0 scores over 6), a phase 3 investigation has been initiated.

In ZENITH, another trial to examine high-risk patients (REVEAL score of 9 or greater), adding sotatercept to background therapy decreased composite mortality, lung transplantation, and hospitalization.

“There is so much excitement about sotatercept in the PAH field,” Dr. Bernardo said. He reviewed interim data from the long-term SOTERIA study, calling attention to the gastrointestinal bleeding events seen in this four-year study, although most bleeding events were mild/moderate.

While most patients with PAH receive systemic phosphodiesterase type 5 inhibitors, such as sildenafil, the INSIGNIA-PAH study evaluated a novel inhaled soluble guanylate cyclase stimulator, which may help circumvent systemic vasodilatory side effects.

Dr. Bernardo underscored the global burden of PAH, pointing out the heterogeneity, even in the United States, in reporting of PAH data into the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) registry.

In a systematic review of GBD data, PAH was associated with a higher disability burden, comparable to that of chronic myeloid leukemia and exceeding that of certain chronic diseases, like multiple sclerosis.

COPD

Sanjay Ramakrishnan, MBBS, FRACP, assistant professor at the University of Western Australia, opened with a remarkable statistic: “65 to 80 percent of adults with COPD in the US and Canada are yet to be diagnosed,” he said. “Case finding in COPD is a big deal, and we don’t do it well enough.”

Dr. Ramakrishnan outlined the “huge effort” undertaken in a Canadian study, which showed that case identification using respiratory care protocols reduced health care utilization, although a large number of people had to be contacted (over 38,000) and tested (2,857) to diagnose one person with COPD.

“Prednisone harms half as many people as it benefits when used to treat all-comers with COPD,” Dr. Ramakrishnan said, setting up the rationale for the ABRA study, in which benralizumab reduced treatment failure to 45 percent from 75 percent with prednisolone in patients with acute exacerbation of asthma or COPD. He added that the health economic analysis from ABRA will be presented at the 2025 European Respiratory Society Meeting.

Randomized studies assessing treatments for severe breathlessness in COPD are sparse, although this is a significant concern for patients and clinicians. Dr. Ramakrishnan discussed a mirtazapine phase 3 randomized trial, which, unfortunately, did not demonstrate efficacy, underscoring the unmet need in this space.

He also highlighted the “clever” and unusual design of a trial evaluating the impact of a reduced cost-sharing and medication-management program on the cost and adherence to maintenance inhaler therapy. Although adherence improved modestly, the rate of COPD exacerbations did not differ between inhaler-eligible Medicare patients randomized within administrative data to receive/not receive an invitation to the program.

Pulmonary Rehabilitation

Tania Janaudis-Ferreira, PhD, BSc (PT), MSc, associate professor at the Research Institute of McGill University Health Center, reviewed the key changes in recommendations in the 2023 ATS clinical practice guidelines for pulmonary rehabilitation (PR). For adults with chronic respiratory conditions, PR is now strongly recommended for patients with stable COPD, with interstitial lung disease, and following hospitalization for COPD exacerbations.

She also reviewed studies on evolving PR concepts, including telerehabilitation for COPD and PR for long COVID.

Dr. Janaudis-Ferreira said that constant work rate cycling, as a measure of exercise endurance, is an underutilized metric in regulatory decision-making, especially in the United States. She highlighted a pooled analysis, which showed for the first time in a cohort of over 5000 patients that exercise training was more effective than bronchodilator therapy across all stages of COPD severity.

PR is underused in COPD practice. In a study from Korea, for instance, only 1.4 percent of eligible patients with stable COPD participated in PR, despite its effectiveness in reducing severe exacerbations and mortality.

Lung Cancer

Nina Thomas, MD, University of Colorado, explored practice-changing evidence across the continuum of lung cancer care, from screening, diagnosis, and treatment to survivorship.

“There is a mortality benefit from annual lung cancer screening for 20 to 24 percent high-risk participants,” Dr. Thomas said. Although screening guidelines are available, the uptake is low, with only 18 percent of eligible people receiving lung cancer screening. Also, current risk-based criteria lack efficiency, cost-effectiveness, and do not account for racial/ethnic disparities. Alternative screening criteria, based on life-years gained, may help reduce disparities and improve sensitivity without losing specificity, especially in former smokers.

Dr. Thomas called out the large variations in diagnostic yield in navigational bronchoscopy and discussed the requirement for a definitive diagnosis in yield calculations in the updated ATS/American College of Chest Physicians guidelines. She also discussed notable changes in the ninth edition of the TNM classification of lung cancer. Oligometastatic disease, for instance, appears to be a continuum without an inflexion threshold per the ninth edition. Therefore, clinical judgement would drive patient selection for localized therapy.

Among treatment advances, Dr. Thomas highlighted a large, randomized trial demonstrating comparable survival with lobar, sublobar, or wedge resections in patients with resectable disease. She also discussed the LAURA study of osimertinib in patients with unresectable stage III epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC).

Dr. Thomas said that the LAURA findings highlight the importance of testing for EGFR mutations during diagnosis and staging, before initiating treatment.

“Lung cancer survival is steadily improving, making survivorship and quality of life increasingly important in lung cancer care,” Dr. Thomas said.

She discussed non-modifiable and modifiable factors—tobacco use, lower BMI, lower physical activity, and comorbidities —identified in a study of quality-of-life predictors in survivors.

“This data helps us focus our survivorship efforts on those who are at high risk of low health-related quality-of-life, and our resources on things we can change,” Dr. Thomas concluded.

This session and the International Conference are supported by independent medical educational grants from Chiesi USA, Inc., Merck & Co., Inc., Olympus Corporation of the Americas, and Verona Pharma, Inc. This session and the International Conference are supported by an in-kind grant from Olympus Corporation of the Americas. All CME sessions have been planned and implemented in accordance with the Accreditation Criteria of the Accreditation Council for Continuing Medical Education (ACCME®) and are free of the control of ineligible companies (formerly commercial interests).