Compared with nonECRSwNP, ECRSwNP has a closer relationship to airway disease such as asthma with broader eosinophilic airway inflammation [25, 26], and tends to have higher incidence rates of asthma and allergic rhinitis [27–29]. Indeed, our findings for the higher incidence rates for asthma, allergic rhinitis and atopy in ECRSwNP patients compared with nonECRSwNP patients in the present study are consistent with the findings of these earlier studies. Then, as patients with ECRSwNP have a greater chance of relapse after surgery, increased rates of postsurgical medication, and poorer quality of life than patients with non-eosinophilic or neutrophilic phenotypes [6–8, 30–32]. Thus, to distinguish CRSwNP as eosinophilic or non-eosinophilic CRSwNP is likely to be important for formulating individualized treatment plans, predicting the prognosis, and reducing recurrence.
Currently, several clinical characteristics such as tissue eosinophils , blood eosinophils , E/M ratio , and the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC)  scores are used to identify ECRSwNP. In the present study, we evaluated the significance of clinical characteristics to differentiate between ECRSwNP and nonECRSwNP. In accordance with findings from other studies [34–36], our study also showed significant differences between the two sub-phenotypes, with respect to symptom scores, E/M ratio, endoscopy scores and blood eosinophils.
Unlike clinical characteristics, biomarkers are considered to be more objective indicators in evaluating ECRSwNP. Some studies have shown Charcot-Leyden crystals (CLCs) to be a marker of eosinophils [37, 38], studies from our group have demonstrated CLCs to be a predictor of ECRSwNP [20, 39]. Unlike CLCs, ALOX15 as a metabolic enzyme, which together with its metabolites plays an important role in eosinophilic inflammation and plays function in epithelial cells on a local metabolic level [11, 15, 17, 19, 40–47]. More recently, a genome-wide association study involving nearly 10,000 NP and CRS patients and over 70,000 controls has indicated that a missense variant in ALOX15 that causes alteration in enzymatic activity confers large genome-wide significant protection against NP . In our study, we found that ALOX15 mRNA level was significantly increased in ECRSwNP patients compared with nonECRSwNP patients and positively associated with tissue eosinophils, olfaction scores, total VAS scores, E/M ratio, endoscopy scores, and blood eosinophils; suggesting that ALOX15 might have predictive significance for ECRSwNP.
Indeed, analysis of ALOX15 mRNA and blood eosinophils by a binary logistic regression model and ROC curve analysis, suggested that ALOX15 might be a valuable predictor of ECRSwNP, as shown by high accuracy, whereas by comparison, blood eosinophils had lower accuracy in predicting ECRSwNP. Moreover, the combination of ALOX15 mRNA and blood eosinophils could improve the accuracy and sensitivity of blood eosinophils in predicting for ECRSwNP, indicated that combining the two factors had an optimal predictive value for ECRSwNP.
Furthermore, analysis of ECRSwNP patients based on the optimal cut-off value of -0.778 for the combination of ALOX15 mRNA and blood eosinophils, the CRSwNP patients with values ≥ -0.778 (high combination group) had significantly higher comorbid asthma, allergic rhinitis, atopy, rhinorrhea scores, olfaction scores, total VAS scores, E/M ratio, endoscopy scores, and blood eosinophils compared with CRSwNP patients with values < -0.778 (low combination group), which were basically consistent with the results of ECRSwNP group mentioned above. As eosinophilic CRS (ECRS) shares many histologic and immunologic features with asthma, it is possible that ECRS and asthma may be influenced by the same immune processes in the upper and lower airways [49–51]. The findings of the present study also support this view and suggest that ALOX15 probably plays an important pathophysiologic role in both the upper and lower airways. Thus, according to the concept of “one airway, one disease”, patients with both ECRSwNP and asthma with increased ALOX15 expression in polyp tissues, would likely benefit from treatment for both diseases.
However, our study has some limitations because of the relatively small sample size and the role of ALOX15 in ECRSwNP only involving the mRNA level. Moreover, only a preliminary inference has been made that ALOX15 might play a role in the upper and lower airways involving ECRSwNP and asthma. Therefore, large sample size is necessary to further verify the predictive value of ALOX15 for ECRSwNP, and to validate the role of ALOX15 in ECRSwNP from multiple levels. In addition, the specific mechanism of ALOX15 in the upper and lower airway inflammation needs to be further studied in the future.