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.