The role of nitric oxide in chronic rhinosinusitis

Abstract

Chronic rhinosinusitis is a very common medical condition that affects nasal and paranasal sinuses mucosa in both adults and children. Its pathology, however, still remains unclear and researchers focus more and more on the role of nitric oxide (NO), a free radical produced in normal conditions by the paranasal sinuses epithelium in healthy patients, in the development of this disease. NO’s role in the upper airway disease is not completely known, but it appears to act like a first-line host defence agent, maintaining the sinuses sterile due to its antiviral and bacteriostatic properties and by increasing mucociliary clearance. NO levels in the exhaled air of patients with CRS are lower than in healthy patients. One explanation for this might be the sinus obstruction that occurs in CRS because subjects with complete sinus opacification have the lowest levels. Furthermore, NO levels decrease after CRS treatments, suggesting that its measurement might help in monitoring the patient’s response to therapy. In this review, we discuss the NO synthesis in the respiratory tract, its involvement in airway pathology, its role in the pathogenesis of CRS and the current clinical uses for NO in CRS and several other airway diseases.

Arginase Isoform Expression in Chronic Rhinosinusitis

“…In patients with CRS, NO levels are reduced. Its decrease is consistent with the severity of the disease, and a concentration increase was noted after therapeutic measures were applied [4,10,32]. The low levels of exhaled and nasal NO found in patients with CRS have been attributed to various mechanisms: (1) sinus ostium obstruction and increased mucosal absorption, injury to the NO-producing sinus mucosa by increased production of cytotoxic agents in chronic inflammation, or (3) decreased iNOS expression caused by certain cytokines, such as IL-4, IL-6, and TGF-β, found in the sinus mucosa of patients with CRS [32,33,34].…”

“…It is produced mainly by the nasal and bronchial epithelial and inflammatory cells under the control of inducible NO synthase (iNOS or NOS2) [22]. NO is part of the first-line host defense mechanisms; its high concentration in the paranasal sinuses can reach up to 23.000 ppb [10], ensuring an antibacterial, antiviral, and antifungal effect. NO increases mucociliary clearance by upregulating ciliary motility; an association between low levels of NO and impaired mucociliary transport has been established [23,24].…”

“…The endogenous biosynthesis of NO is the result of L-arginine oxidation, a reaction catalyzed by inducible nitric oxide synthase (NOS) (Figure 1). L-arginine is an amino acid also used by arginase (ARG) in the urea cycle to form urea and ornithine [10], thus the two enzymes are competing for the same substrate. Arginase exists in two isoforms: arginase-1 (ARG1) and arginase-2 (ARG2).…”