Exhaled Nitric Oxide as Biomarker of Type 2 Diseases

Abstract

Nitric oxide (NO) is a short-lived gas molecule which has been studied for its role as a signaling molecule in the vasculature and later, in a broader view, as a cellular messenger in many other biological processes such as immunity and inflammation, cell survival, apoptosis, and aging. Fractional exhaled nitric oxide (FeNO) is a convenient, easy-to-obtain, and non-invasive method for assessing active, mainly Th2-driven, airway inflammation, which is sensitive to treatment with standard anti-inflammatory therapy. Consequently, FeNO serves as a valued tool to aid the diagnosis and monitoring of several asthma phenotypes. More recently, FeNO has been evaluated in several other respiratory and/or immunological conditions, including allergic rhinitis, chronic rhinosinusitis with/without nasal polyps, atopic dermatitis, eosinophilic esophagitis, and food allergy. In this review, we aim to provide an extensive overview of the current state of knowledge about FeNO as a biomarker in type 2 inflammation, outlining past and recent data on the application of its measurement in patients affected by a broad variety of atopic/allergic disorders.

Keywords: COPD; allergy; asthma; biomarkers; mediators; outcome.

Figure 1

Schematic representation of the Th2 pathway. Dendritic cell activation by damaged epithelial cells secreting interleukin (IL)-4 prompts Th0 cells to differentiate into Th2 cells. Th2 cells secrete IL-5, among other cytokines, which represents the main stimulus for the production and recruitment of eosinophils (orange arrow) at the level of the target organ. Infections or exposure to pollutants induce epithelial cells to release the so-called alarmins (IL-25, IL-33, thymic stromal lymphopoietin (TSLP)) which activate innate lymphoid cells 2 (ILC2), which produce Th2 cytokines. IL-13, mainly secreted by eosinophils, activates the expression (orange arrow) of inducible nitric oxide synthase (iNOS) and increases the production of NO. AR, allergic rhinitis; CRS, chronic rhinosinusitis; EoE, eosinophilic esophagitis; AD, atopic dermatitis.