Navigating Severe Asthma Management Without Direct TSLP Biomarkers

"Navigating Severe Asthma Management Without Direct TSLP Biomarkers" takes up the question of what clinicians cannot currently measure.

Dr. Chupp puts two questions to Dr. Hanania. Do particular biomarker patterns change how he treats a patient? And given that alarmins are now considered important targets, is there any biomarker for them, or anything on the horizon? Dr. Hanania first adds a use his colleagues did not mention. Beyond prediction and pharmacodynamic response, he uses biomarkers prognostically, to identify patients at risk of exacerbation, and notes emerging data suggesting composite biomarkers may predict that risk better than single ones.

On alarmins, his answer is direct: no specific biomarker exists, particularly for TSLP. But he offers a workaround rooted in the pathway. Because TSLP drives downstream signaling, blocking it lowers IgE, eosinophils, and FeNO. So while FeNO reflects the IL-13 pathway specifically, a master regulator sitting above all three pathways is reflected, indirectly, in all three of the biomarkers already available. He knows of nothing in the pipeline specific to TSLP or IL-33, and notes these cytokines are not easily measured, so clinicians cannot identify a high-TSLP patient and target accordingly.

He then returns to the non-type 2 gap. Epithelial cytokines act on that pathway too, but the measurement tools are poor. Airway neutrophils have been examined and are not as good as sputum or blood eosinophils. He calls biomarkers reflecting non-type 2 inflammation a major unmet need, made more pressing precisely because TSLP influences that pathway.

Dr. Hanania closes by agreeing with the overlap point. Isolated high eosinophils with a predominant IL-5 pathway occur, but in allergic and non-allergic type 2 asthma all the markers are often elevated together. Deciding which pathway predominates, he admits, is usually a guessing game.

In "Low T2 Asthma: What Anti-TSLP Data Show in Low-Eosinophil Patients," the panel will examine what the trial data show in patients whose biomarkers stay low.