COPD Novel Biomarkers Might Improve Monitoring and Treatment

VIENNA — Documenting airway thickness in patients with chronic obstructive pulmonary disease (COPD) can help physicians target eosinophilic airway inflammation with biologics, researchers suggested at the European Respiratory Society (ERS) 2024 Congress.
Federico Baraldi, PhD, a researcher in respiratory medicine at the University of Ferrara, Ferrara, Italy, and current research fellow at Imperial College of London, United Kingdom, told Medscape Medical News that CT scans are underutilized in assessing airway thickening and inflammation, which are critical for identifying patients who may benefit from biologic treatments. “Eosinophil counts are not consistently accompanied by imaging studies like CT scans to provide a full picture of the disease,” he said.
In separate research presented at the ERS 2024 Congress, scientists have identified biomarkers of COPD exacerbation in patients’ breath to predict and prevent episodes.
“There is no effective tool to predict COPD exacerbations before they occur,” Jorrit van Poelgeest, a PhD candidate at Amsterdam UMC in The Netherlands, told Medscape Medical News. This leads to reactive treatment rather than proactive management. His group is developing a tool that allows patients to monitor compounds in their breath and act early on upcoming exacerbations.
Eosinophilia and Airway Thickness
Researchers recruited 100 participants from the London COPD Exacerbation Cohort. They measured blood eosinophil counts (BEC) annually for 4 years during stable periods and collected exacerbation data before oral corticosteroid treatment. They classified patients based on their eosinophilic status:
Persistent Eosinophilic group — BEC > 300 in at least three visits but not < 250 in all visits
Intermittent Eosinophilic group — BEC > 300 in at least one visit but < 250 in at least one visit
Never Eosinophilic group — BEC < 300 in all four visits
All participants underwent quantitative CT scans, which were analyzed for airway lumen-to-wall thickness ratio (Pi10), emphysema, air trapping, and ground glass opacity.
The results, presented at the ERS 2024 Congress, showed that the Pi10 index was significantly higher in the Persistent Eosinophilic group than in the Never and Intermittent Eosinophilic groups. Researchers found no differences between these groups in air trapping, emphysema, or ground glass opacity. There was no significant difference in Pi10 between Eosinophilic Exacerbators and Non-Eosinophilic Exacerbators.
These findings suggest that persistent eosinophilia in COPD is associated with increased airway wall thickness, said Baraldi. This could have important clinical implications, as it raises the question of whether targeting eosinophilic airway inflammation could modify airway thickness in COPD patients. “We are entering the era of biologic treatments, and without a CT scan, we may miss a lot of valuable information,” said Baraldi.
He said inhaled corticosteroids do not significantly impact airway thickening (Pi10), indicating the need for better-targeted therapies, such as biologics. “Biologic therapies like dupilumab will become available soon for COPD patients, making it important to have biomarkers like Pi10 to track the effect of treatment.”
Volatile Biomarkers for COPD Exacerbation
In another study presented at the ERS 2024 Congress, researchers identified volatile organic compounds (VOCs) associated with COPD exacerbations as potential biomarkers for early detection and monitoring.
The researchers conducted a systematic literature search across multiple databases to identify relevant VOCs. They then validated these VOCs using data from the TEXACOLD trial, which included longitudinal samples from 14 COPD patients at three timepoints: At baseline, during exacerbation, and during follow-up.
The search yielded 12 candidate VOCs. These were analyzed using gas chromatography–mass spectrometry on 42 samples from the TEXACOLD trial participants. The data was then processed using sparse partial least-squares discriminant analysis (sPLSDA) and Wilcoxon testing.
The resulting sPLSDA model showed that the VOC profile changes substantially when a patient experiences an exacerbation, suggesting that the identified VOCs could serve as biomarkers for detecting the onset of an exacerbation. The VOC profile changes again as the patient recovers from the exacerbation. This could be useful for monitoring recovery and determining when a patient has returned to their baseline. The VOC profile returns to a state similar to the pre-exacerbation baseline after recovery. This is important because it indicates that the changes in VOCs during an exacerbation are temporary and reversible.
These findings suggest that the identified VOCs could be biomarkers for detecting COPD exacerbations.
Currently, these analyses are done by gas chromatography, but the researchers are developing an at-home device that can analyze patients’ breath and give real-time results.
Van Poelgeest and Baraldi reported no relevant financial relationships.
Manuela Callari is a freelance science journalist specializing in human and planetary health. Her words have been published in The Medical Republic, Rare Disease Advisor, The Guardian, MIT Technology Review, and others.
 
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