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.