4. discussion
ILC2s in sinonasal tissues play critical roles in eosinophilic inflammation by producing type 2 cytokines in eCRS patients. Our previous study revealed that the ILC2 prevalence in sinonasal tissues is positively correlated with the number of tissue-infiltrating eosinophils16. It has also been reported that the ILC2 prevalence in sinonasal tissues is positively correlated with nasal symptom scores in CRS patients13, and that SCS reduce the ILC2 prevalence in eosinophilic nasal polyps14. In the present study, the ILC2 prevalence in sinonasal tissues was correlated with that in preoperative blood in the eCRS and non-eCRS patients, but was not correlated with the pre- or postoperative LMK-CT scores. Postoperatively, the ILC2 prevalence in blood was decreased, and it was associated with a good outcome (LMK-CT score improvement rate ≥50%) after ESS. This is the first report to show a correlation between the ILC2 prevalence in tissue and in blood and the clinical outcome after ESS in eCRS and non-eCRS patients, and to show that a decreased ILC2 prevalence in postoperative blood is associated with a good postoperative outcome after ESS.
Tissue ILC2s are important in eosinophilic inflammation; however, the role of ILC2s in blood is not well understood. In patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD), the ILC2 prevalence is increased in nasal scraping samples, but decreased in blood at the time of cyclooxygenase-1 inhibitor reactions15. ECRS is often comorbid with N-ERD. Similarly, segmental allergen challenge in patients with allergic asthma results in increased numbers of ILC2s in bronchoalveolar fluids and decreased numbers of ILC2s in blood16. These results suggest that ILC2s may be recruited from blood to the airway in response to allergen exposure. In the present study, the ILC2 prevalence in blood did not differ between the eCRS and non-eCRS patients before and after ESS, whereas the ILC2 prevalence in sinonasal tissues was increased in the eCRS patients when compared to the non-eCRS patients (Table 1), and was positively correlated with the ILC2 prevalence in preoperative blood.
We previously revealed that the ILC2 prevalence in blood is increased in patients with AR11, and it also has been reported that the prevalence is positively correlated with the serum IL-13 levels17. The ILC2 prevalence in blood is increased during pollen season in patients with grass pollen-induced AR, and it is decreased after subcutaneous allergen-specific immunotherapy18. Increased levels of blood ILC2s have also been reported in asthmatic patients19,20.21, and the increased levels of IL-13+ ILC2s in the blood of uncontrolled asthmatic patients decrease when the asthma is well-controlled20. These results suggest that effective therapeutic interventions result in a decrease of blood ILC2s in patients with AR and bronchial asthma. Similar to previous studies that reported no increase in the ILC2 prevalence in the blood of eCRS patients11,22, our present study also showed that the ILC2 prevalence in preoperative blood was not increased in the eCRS patients when compared to the non-eCRS patients. All patients received macrolide therapy, muco-active drug, and nasal saline irrigation, and there were apparent differences in the postoperative treatments between the eCRS and non-eCRS patients. All eCRS patients used INCS for a long time, and more than half of them used anti-leukotrienes and SCS. Despite these differences, the ILC2 prevalence in blood and the LMK-CT score were significantly decreased after ESS in both the eCRS and non-eCRS patients. Although these postoperative therapies in eCRS patients may affect the postoperative decrease in the ILC2 prevalence in blood, it is interesting to note that the ILC2 prevalence in blood was also decreased in the non-eCRS patients who were not treated with such eosinophilic inflammation-suppressing therapy. It has been reported that type 2 inflammation is partially involved in non-eCRS23, and surgical intervention may attenuate type 2 inflammation even in non-eCRS patients.
We evaluated the postoperative outcomes of CRS patients using the LMK-CT score at an average of 14 months after ESS, and the CRS patients were divided into a good outcome group and a poor outcome group. The ILC2 prevalence in blood at an average of 6 months after ESS was decreased in the good outcome group, but not in the poor outcome group. These results indicate that a decreased ILC2 prevalence in postoperative blood may predict a good postoperative outcome after ESS. Further studies using symptom scores, such as SNOT-22, to evaluate the clinical efficacy after ESS are of interest.
In conclusion, the ILC2 prevalence in sinonasal tissues was correlated with that in preoperative blood in eCRS and non-eCRS patients. The ILC2 prevalence in blood was decreased after ESS, and it was associated with a good outcome as evaluated by the LMK-CT scores. These results suggest that a decreased ILC2 prevalence in blood after ESS may predict a good postoperative outcome in eCRS and non-eCRS patients.