Nasal Nitric Oxide in Chronic Rhinosinusitis with or without Nasal Polyps: A Systematic Review with Meta-Analysis

Abstract

Background and Aims: There has been a recent growing interest in the role of nasal nitric oxide (nNO) as a biomarker for osteomeatal complex obstruction in paranasal sinus diseases. By using meta-analysis, we systematically reviewed the literature to establish the possible link between nNO concentration and chronic rhinosinusitis with nasal polyps (CRSwNP) or without (CRSsNP). Methods: We systematically searched the EMBASE, PubMed, Scopus, and Web of Science databases for related studies. Differences between controls and cases were reported as standardized mean difference (SMD), with 95% confidence intervals (95% CI), using the random-effects method. Results: We selected 23 articles for the final analysis: 15 with data on 461 CRSwNP patients and 384 healthy controls, 10 with data on 183 CRSsNP patients and 260 controls, and 14 studies on 372 CRSwNP and 297 CRSsNP patients. CRSwNP patients showed significantly lower nNO values when compared to both healthy controls (SMD: −1.495; 95% CI: −2.135, −0.854; p < 0.0001) and CRSsNP patients (SMD: −1.448; 95% CI: −2.046, −0.850; p < 0.0001). Sensitivity and subgroup analyses confirmed the results, which were further refined by regression models. They showed that an increasing aspiration flow is related to a greater difference in nNO levels between cases and control subjects. We also documented lower nNO levels in CRSsNP patients with respect to controls (SMD: −0.696; 95% CI: −1.189, −0.202; p = 0.006), being this result no longer significant when excluding patients in therapy with intranasal corticosteroids. As shown by regression models, the increased Lund–Mackay score indicates a high effect size. Conclusions: nNO levels are significantly lower in CRSwNP, especially when using higher aspiration flows. Additional studies are needed to define one single standardized method and normal reference values for nNO.

Performance of fractional exhaled nitric oxide in predicting response to inhaled corticosteroids in chronic cough: a meta-analysis

“…In brief, eosinophilic airway inflammation derives from the activation of mast cells and antigen-specific T helper 2 cells, with the concomitant production of cytokines, such as interleukin (IL)-4, IL-5 and IL-13 [ 10 ]. Their release regulates the expression of the inducible isoform of NO synthase (iNOS), thus determining an increased NO production in an allergic environment [ 11 ]. This implies that FeNO assessment may be able to accurately predict eosinophilic airway inflammation - a peripheral trigger of cough reflex with a good ICS response - in a rapid, non-demanding and cost-effective manner [ 54 ].…”

“…Past observation that the nitric oxide (NO) concentration in exhaled air generally increases in chronic inflammatory airway diseases [ 10 , 11 ] has led the European Respiratory Society (ERS) and the American Thoracic Society (ATS) to agree on highly standardised procedures to measure fractional exhaled NO (FeNO) [ 12–14 ]. Thus, FeNO has become an important non-invasive support to monitor compliance and efficacy of steroids in chronic airway diseases, especially asthma [ 15 , 16 ].…”

Predictive and Diagnostic Value of Nasal Nitric Oxide in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps

“…Frendø et al [28] found that in patients with CRSwNP, nNO levels were significantly lower than those in the controls. A meta-analysis by Ambrosino et al [29] also revealed that compared with healthy controls, CRSwNP patients showed significantly lower nNO levels. Similar to previous research, our results also showed that patients with CRSwNP had lower nNO levels compared with the healthy controls.…”

The Functional Diversity of Nitric Oxide Synthase Isoforms in Human Nose and Paranasal Sinuses: Contrasting Pathophysiological Aspects in Nasal Allergy and Chronic Rhinosinusitis

“…Negative correlations have been observed between nasal NO levels and the severity of sinus infection, as indicated by computed tomography (CT) scores or nasal polyp scores [ 59 , 112 , 115 , 116 , 117 ]. Ambrosino et al recently performed a systematic review to investigate the possible link between the nasal NO concentration and CRS phenotypes, and they reported that CRSwNP patients showed significantly lower nasal NO values compared to those of both healthy controls and CRSsNP patients, based on 23 selected articles [ 118 ]. Interestingly, the observed difference in nasal NO levels was related to the flow rate of the nasal aspiration, with the difference between cases and control subjects being more prominent when higher aspiration flows were used.…”

“…On the other hand, it remains controversial whether a link exists between nasal NO levels and the severity of ECRS, due (probably) to the multifunctional roles of NO [ 118 ]. A recent study reported that nasal NO levels determined by subtracting the nasal FeNO level from the oral FeNO level were significantly lower in the CRS group (both ECRS and non-ECRS) than in the control group, with the ECRS group’s difference being more prominent [ 112 ].…”