Molecular Th2 Phenotypes of Asthma: New Biomarker or NO?

Abstract

To the Editor: I believe that a noninvasive biomarker already exists for the T-helper type 2 (Th2)–high and Th2–low molecular subphenotypes of asthma reported by Dr. Woodruff and colleagues (1). The authors showed that lung function improvements with inhaled corticosteroids (ICS) were restricted to Th2-high asthma, which had greater airway hyperresponsiveness, eosinophilia, and remodeling, and they concluded that future work should be directed at identifying noninvasive biomarkers that correlate with these molecular phenotypes. Presumably, the UCSF airway tissue bank did not have information regarding the exhaled nitric oxide (NO) of subjects, insofar as it was not shown. Unfortunately, it was also not discussed. Exhaled NO has shown to correlate with response to steroids, increased airway hyperresponsiveness to methacholine, and eosinophilic inflammation of the airways in asthma as well as mouse models of the asthmatic processes (2–4). Whether exhaled NO can be a marker of airway remodeling is less clear. In one study, exhaled NO was also found to correlate with several parameters of airway remodeling in children with refractory asthma (5). Thus high exhaled NO is reminiscent of Th2-high. Low exhaled NO predicts poor response to ICS similar to Th2-low and is associated with either paucity of inflammatory cells in the airway or noneosinophilic inflammation. Despite recent controversies regarding clinical use of exhaled NO, it has probable utility in the asthma management algorithm, including when it is low (6). I hope that similar use will emerge for these molecular phenotypes and look forward to further investigations testing their comparative ability to characterize asthma in a model that includes exhaled NO.