The third session of the Clinical Year in Review series on Tuesday, May 20, at the ATS 2025 International Conference took a deep dive into the latest research and therapeutic advances in bronchiectasis, interstitial lung disease (ILD), lung transplant, and pulmonary infections.

Bronchiectasis

Beth Shoshana Zha, MD, PhD, assistant clinical professor at the University of California San Francisco, highlighted the heterogeneity and multiple etiologies underlying bronchiectasis and the spectrum of associated complications.

Dr. Zha reviewed data for dipeptidyl peptidase 1 (DPP1) inhibitors, BI 1291583 and brensocatib, noting that BI 1291583 is now in phase 3 studies, and brensocatib is under FDA review based on data from the ASPEN study.

Cystic fibrosis (CF) is a leading cause of bronchiectasis. CF transmembrane conductance regulator (CFTR)-targeted therapies have revolutionized CF care. Contextualizing the SKYLINE studies of vanzacaftor-tezacaftor-deutivacaftor (VTD), Dr. Zha said, “The question remains, ‘Can we do better?’”  VTD was non-inferior to elexacaftor-tezacaftor-ivacaftor in terms of percent predicted forced expiratory volume (FEV1) and, “excitingly, VTD was superior in reducing sweat chloride.”

Primary ciliary dyskinesia (PCD), a rare autosomal recessive disorder, is another cause of bronchiectasis. A nebulized epithelial sodium channel blocker, idrevloride, improved lung function in people with PCD in the CLEAN-PCD crossover trial.

Dr. Zha encouraged the audience to read the 2024 International Society for Human and Animal Mycology guidelines for allergic bronchopulmonary aspergillosis, highlighting key aspects of the evidence base and recommendations.

“People with bronchiectasis have a 20 to 50 percent chance of having chronic infection with Pseudomonas aeruginosa, and when it occurs, it increases risk of exacerbation and mortality,” Dr. Zha said. She reviewed findings from the PROMIS-I and II studies of inhaled colistimethate sodium, notably the improvements in exacerbation rates, time to first exacerbation, and quality of life in PROMIS-II.

Interstitial Lung Disease

“It is a privilege to kick off what, to me, is the most consequential session on ILD in decades,” said Ayodeji O. Adegunsoye, MD, PhD, MS, assistant professor of medicine at the University of Chicago. He covered five major themes: early detection and risk stratification, molecular and epigenetic profiling, genomic testing in clinical practice, idiopathic pulmonary fibrosis (IPF) symptom management, and therapeutic innovation and trial design.

Minor interstitial lung abnormalities (ILAs) frequently represent subclinical ILD in patients at risk of familial pulmonary fibrosis, according to a prospective cohort study. Dr. Adegunsoye said this may mean that the current five percent threshold for ILAs misses biologically active, clinically relevant disease.

Molecular/epigenetic profiling of plasma biomarkers may improve clinical classification of IPF and help identify patients likely to benefit from therapy.

Dr. Adegunsoye made a case for broadening access to genetic counseling and cascade genetic testing, as well as prospective trials assessing how telomere length impacts survival in ILD, based on a recent study showing that incorporating telomere length testing informed treatment decisions in one-third of patients with ILD.

The PACIFY-COUGH trial helped identify a treatment option that provides “clinically meaningful outcomes in a disease without any proven tools or treatments,” Dr. Adegunsoye noted. In the study, morphine reduced IPF-related cough. Moreover, patients reported feeling better and adherence was nearly 100 percent.

The FIBRONEER studies in IPF and ILD are “two massive studies with over 1000 patients across 45 countries, which can provide highly generalizable” findings, Dr. Adegunsoye said, in his discussion of innovation and trial design in ILD.

FIBRONEER-IPF findings, first reported at ATS 2025 in the Breaking News session on Monday, May 19, showed reduced decline in lung function with nerandomilast over placebo.

Lung Transplant

Michaela R. Anderson, MD, MS, assistant professor of medicine at the University of Pennsylvania School of Medicine, illustrated clinical advances impacting lung transplant medicine using a case study.

Lung transplant survival is lower in adults and children compared to other solid organ transplants. The higher mortality is driven primarily by injury to the transplanted lung, via primary graft dysfunction (PGD) or late chronic lung allograft dysfunction (CLAD).

Dr. Anderson discussed a study suggesting that smoking-related PGD may represent a less severe phenotype of lung injury, as donor smoke exposure increases PGD risk but does not impact post-transplant survival.

Dr. Anderson discussed the choice between extracorporeal membrane oxygenation and cardiopulmonary bypass, with a focus on the 2024 consensus from the International Society for Heart and Lung Transplantation, and the optimal post-transplant immunosuppressive regimen, tacrolimus or cyclosporin.

Donor-derived cell-free DNA (dd-cfDNA) may be a marker of allograft injury, and extreme increases in dd-cfDNA may signal increased risk of CLAD and death, according to a small study. Although dd-cfDNA is not yet ready for prime time, these data represent an “exciting step forward for the field,” Dr. Anderson concluded.

Pneumonia and Pulmonary Infections

Chiagozie Pickens, MD, MSci, assistant professor of medicine at Northwestern University Feinberg School of Medicine, spoke about community-acquired and nosocomial pneumonia, tuberculosis, and viral infections.

“Pneumonia is the leading cause of death from infection and appropriate management requires an accurate and reproducible diagnosis,” Dr. Pickens said, introducing a study conducted at Veterans Affairs medical centers. She highlighted the high diagnostic discordance, clinician uncertainty around pneumonia diagnosis, and treatment ambiguity in the study.

Dr. Pickens discussed the REGARD-VAP individually randomized trial, which showed that patient-tailored short courses of antibiotics may be suitable for some patients with ventilator-induced pneumonia.

Treatment options for rifampin-resistant tuberculosis are limited. Moreover, injected aminoglycoside/polypeptide therapies for rifampin-resistant disease require long-term use and cause significant toxicity.

Three all-oral shorter-duration regimens demonstrated efficacy in rifampin-resistant tuberculosis in the endTB study. The WHO endorsed these regimens in 2024, Dr. Pickens noted.

Dr. Pickens highlighted the importance of respiratory syncytial virus (RSV) vaccination in preventing upper respiratory disease and RSV-associated hospitalizations and emergency department encounters, reviewing new real-world evidence.

She concluded by spotlighting 2024 sporadic human avian influenza A(H5N1) cases, which occurred predominantly in people exposed to infected animals and were characterized by mild illness. To date, “human-to-human transmission has not been documented,” Dr. Pickens said.

This session and the International Conference are supported by independent medical educational grants from Boehringer Ingelheim Pharmaceuticals, Inc., Insmed Incorporated, Vertex Pharmaceuticals, Inc., and Zambon. 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).