Bentham Science Newsletter

Respiratory Medicine Spotlight | Bentham Science

In this issue, we take a look at recent news on respiratory medicine.

AI‑Designed Drug Offers New Hope in Lung Fibrosis

An international team led by Insilico Medicine has achieved a milestone: the first proof-of-concept clinical trial of a drug entirely discovered and designed using generative AI. The study tested rentosertib, a novel small-molecule inhibitor targeting TNIK, in patients with idiopathic pulmonary fibrosis (IPF), a progressive lung disease with poor prognosis

In a 12-week, phase 2a randomized, double-blind, placebo-controlled trial involving 71 participants, rentosertib was well tolerated across all doses. Importantly, the highest dose (60 mg once daily) showed promising efficacy—patients experienced an average increase of +98.4 mL in forced vital capacity (FVC), while the placebo group saw a decline of −20.3 mL Adverse events were mostly mild and consistent across groups.

These results validate the potential of generative AI both in target identification (TNIK) and molecule design, marking a significant shift in drug discovery. The success of rentosertib encourages larger and longer trials, and could revolutionize how novel therapies are created for fibrotic and other complex diseases.

Beyond the Breath Test: New COPD Diagnostic Model Highlights Hidden Risk

A groundbreaking study published in JAMA introduces a new multidimensional diagnostic approach for Chronic Obstructive Pulmonary Disease (COPD), revealing that many at-risk individuals could be missed by current spirometry-only criteria. By incorporating respiratory symptoms, quality of life assessments, and CT imaging findings like emphysema and bronchial wall thickening, researchers were able to more accurately identify individuals at risk of serious outcomes.

In two large cohorts (COPDGene and CanCOLD), 15.4% of people without airflow obstruction by spirometry were newly diagnosed with COPD under the new model. These reclassified individuals showed significantly higher risks of death, more exacerbations, and faster lung function decline. Conversely, some with airflow obstruction but no symptoms or imaging abnormalities were no longer classified as having COPD.

This redefinition of COPD provides a more nuanced, personalized diagnostic tool that could guide earlier intervention and better outcomes. It emphasizes that normal spirometry doesn’t always mean normal lungs—advanced imaging and symptom tracking matter.

New PET Imaging Technique Catches Pulmonary Hypertension Early

A novel imaging approach using 18F-FAPI PET scans can detect early signs of pulmonary arterial hypertension (PAH)—a progressive condition that damages the arteries in the lungs. Researchers from the First Affiliated Hospital of Guangzhou Medical University found that increased uptake of 18F-FAPI, which binds to activated fibroblasts (key players in tissue remodeling), correlates with disease severity and cardiac dysfunction.

In both animal models and a human study involving 38 patients, 18F-FAPI PET revealed fibroblast activity well before structural changes became irreversible. Among patients receiving PAH-targeted therapy, reduced 18F-FAPI uptake was associated with clinical improvement, showing the scan’s potential for tracking treatment response.

This imaging advancement could revolutionize PAH care by enabling earlier diagnosis, real-time therapy monitoring, and personalized treatment planning—a critical step forward in managing a life-threatening disease.

When Coughs Affect the Brain: RSV and Influenza’s Hidden Neurological Risks in Children

Respiratory Syncytial Virus (RSV) and influenza are leading causes of seasonal respiratory infections in children — but their impact extends beyond the lungs. Both viruses can trigger serious neurological complications, particularly in vulnerable children with pre-existing conditions. Common symptoms include seizures, encephalitis, headaches, and in more severe cases, stroke and acute necrotizing encephalopathy.

Research reveals that up to 10–30% of children with influenza and 1.2–1.8% of RSV-infected children may develop neurological issues, often via hematogenous or retrograde neural pathways. RSV-related issues may also include central apnea, feeding difficulties, ataxia, and CSF abnormalities, with long-term consequences such as learning impairments.

This review highlights the urgent need for enhanced surveillance, better prevention strategies, and targeted therapies to protect developing brains from these common — but potentially devastating — viruses.

Cytomegalovirus: A Hidden Player in Lung Disease and Mortality Risk?

Cytomegalovirus (CMV), often silent in healthy individuals, is gaining attention for its potential role beyond traditional infections. A recent mini-review in Current Respiratory Medicine Reviews explores CMV’s impact on immunosenescence—age-related immune decline—and its association with increased all-cause mortality, including cardiovascular, oncological, and respiratory deaths.

Importantly, the review delves into CMV’s emerging link with obstructive lung diseases, such as COPD. CMV infections, like other viruses, may trigger exacerbations or even contribute to the development and progression of chronic pulmonary conditions. Evidence suggests that CMV seropositivity could serve as a biomarker for risk stratification or represent a novel therapeutic target in chronic respiratory illness.

Though findings remain mixed, the review highlights the urgent need for further research into CMV’s role in chronic lung diseases and its broader impact on long-term health outcomes.