Breathomics, plasma lipidomics predict responses to omalizumab in asthma

Key takeaways:

• During omalizumab treatment, volatile organic compounds and plasma lipids “strongly predicted” fewer exacerbations.
• These biomarkers could also tell severe asthma apart from mild asthma.

Among patients with severe asthma receiving omalizumab, breathomics and plasma lipidomics predicted early and late treatment responses, according to results published in American Journal of Respiratory and Critical Care Medicine.

“Development of these biomarkers has significant potential to give patients, their medical teams and payers more certainty of achieving reduced exacerbations with omalizumab, a key objective of asthma treatment,” Ratko Djukanovi, MD, DM, FRCP, FERS, professor of medicine at the University of Southampton, and colleagues wrote.

In the real-world, open-label study of mechanisms of action of omalizumab in severe asthma (SoMOSA), Djukanovi and colleagues assessed 191 patients with severe uncontrolled atopic asthma receiving high-dose inhaled corticosteroids and long-acting beta-agonists to determine if there are biomarkers that can predict improvement while on omalizumab for up to 16 weeks and from 16 to 52 weeks.

Researchers used Global Evaluation of Therapeutic Effectiveness (GETE) to identify early clinical improvement among those who received omalizumab for 16 weeks and found this outcome in 121 (63%) patients.

From the total cohort, 173 patients went on to receive omalizumab for 52 weeks. Between 16 weeks and 52 weeks, researchers found that more than 50% of patients had at least a 50% reduction in exacerbations (n = 120; 71%) and maintenance oral corticosteroid dose if on this treatment (37 of 65 patients; 57%).

During the search for biomarkers that predict GETE (early response) and/or exacerbation reductions (late response) while on omalizumab, several biomarkers failed at making these predictions: 2,3-dinor-11-beta-prostaglandin F2 alpha, GETE, blood and sputum eosinophils, exhaled nitric oxide and serum IgE.

However, based on receiver operating characteristic area under the curve (AUC), researchers found strong prediction of fewer exacerbations with five plasma lipids (AUC, 0.922) and five volatile organic compounds (2-ethyl-1-hexanol, toluene, 2-pentene, nonanal and one with an unknown identity; AUC, 0.78).

The same types of biomarkers also “strongly predicted” early responses, with an AUC of 0.949 with use of five plasma lipids and an AUC of 0.835 with use of volatile organic compounds benzothiazole, acetophenone, 2-pentyl-furan, methylene chloride and 2-methyl-butane, according to researchers.

Notably, researchers could tell severe asthma apart from mild asthma in a different cohort of patients using some of the above predictive biomarkers.

“The identified biomarkers should be viewed as candidate biomarkers that require confirmation in a prospective study in which treatment efficacy in patients selected by these biomarkers would be compared with efficacy in patients selected by standard clinical criteria,” Djukanovi and colleagues wrote.

“Prospective validation of the candidate biomarkers should focus on breathomics, an easy to apply platform, or in combination with plasma lipid measurements,” Djukanovi and colleagues added.