1. objectives
Chronic rhinosinusitis (CRS) is characterized by persistent symptomatic inflammation of the nasal and paranasal mucosa that lasts longer than 12 weeks1. CRS can be further classified into two major subtypes: CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP)1. In the United States and European countries, CRSsNP presents as the predominant infiltration of neutrophils and type 1 or type 3 cytokines, whereas CRSwNP is characterized by eosinophilic infiltration and type 2 cytokines. However, the phenotypes of inflammation in CRSwNP differ between European and East Asian countries. Half of CRSwNP cases in Japan exhibit neutrophilic inflammation2, and CRSwNP patients in other East Asian countries also represent both eosinophilic and neutrophilic phenotypes3,4. For the diagnosis of eosinophilic CRS (eCRS), a novel scoring system and algorithm were established based on the assessment of bilateral disease, nasal polyp formation, ethmoid sinus-dominant computed tomography (CT) shadows, and blood eosinophilia in the Japanese Epidemiological Survey of Refractory Eosinophilic CRS (JESREC) study. ECRS is characterized by marked eosinophilia in nasal polyps, and is associated with greater clinical and radiological severity, higher morbidity with bronchial asthma, and a higher risk of polyp recurrence when compared to non-eCRS5.
The Lund-Mackay CT scan (LMK-CT) score6 is the most commonly used metric for evaluating the radiological severity of CRS1. Preoperative LMK-CT scores have been shown to be positively correlated with a nasal component of the 22-Item Sino-Nasal Outcomes Test (SNOT-22), a validated disease-specific survey for the quality of life7. For the treatment of CRS, intranasal corticosteroids (INCS) and nasal saline irrigation are the mainstays1, and low-dose and long-term 14- and 15-membered macrolides (macrolide therapy) are widely used in Japan8. When such conservative treatments fail, endoscopic sinus surgery (ESS) is performed. Due to the high postoperative recurrence rate in eCRS patients, there is a need for an index to predict the postoperative outcomes.
Group 2 innate lymphoid cells (ILC2s) are important effector cells for type 2 immune responses in eosinophilic airway inflammation, such as eCRS, allergic rhinitis (AR), and bronchial asthma9. Environmental allergens induce the rapid release of epithelial-derived cytokines, such as interleukin (IL)-33, IL-25, and thymic stromal lymphopoietin; in response to these cytokines and to lipid mediators, such as prostaglandin D2 and cysteinyl leukotrienes, ILC2s in mucosal tissues quickly produce large amounts of IL-5 and IL-13, leading to airway eosinophilia, mucus production, and tissue repair10. We previously reported that the ILC2 prevalence in sinonasal tissues is increased in eCRS patients, and is positively correlated with the number of infiltrating eosinophils, but that the ILC2 prevalence is not increased in the peripheral blood of eCRS patients11. Although the importance of ILC2s in sinonasal tissues is well-known, the impact of ILC2s in peripheral blood has not yet been thoroughly investigated in CRS patients.
This study aimed to determine whether the ILC2 prevalence in sinonasal tissues and in peripheral blood is associated with the postoperative outcomes in CRS. The CRS cases were classified as eCRS or non-eCRS according to the JESREC study. The disease severity and postoperative outcome were evaluated using the LMK-CT scores at an average of 14 months after ESS. The ILC2 prevalence in postoperative blood was examined at an average of 6 months after ESS to determine whether the changes in the ILC2 prevalence in blood are associated with the postoperative outcome.