Serum YKL-40 Levels Predict Endotypes and Associate with Postoperative Recurrence in Patients with Chronic Rhinosinusitis with Nasal Polyps

Figures & data

Table 1 The Demographic and Clinical Characteristics of Subjects

Parameters	HC (n=40)	neCRSwNP (n=43)	eCRSwNP (n=37)	P value
Age, years	43.3±12.5	43.1±9.1	43.8±10.2	0.976
Gender (male/female)	23/17	26/17	22/15	0.962
Smoking (yes/no), n	10/30	13/30	9/28	0.802
Drinking (yes/no), n	7/33	4/39	4/33	0.493
BMI, kg/m^2	23.1±2.3	23.3±1.6	23.5±1.9	0.815
Allergic rhinitis (yes/no), n	0/40	4/39	11/26	<0.001
Asthma (yes/no), n	0/40	2/41	6/31	0.014
Blood eosinophil counts (10^9/L)	0.2±0.1	0.3±0.1	0.4±0.2	<0.001
Blood eosinophil percentage (%)	2.5±0.7	2.7±1.0	3.3±1.2	<0.001
Preoperative VAS score	NA	5.6±2.0	6.1±1.6	0.344
Preoperative Lund–Mackay score	NA	9.5±1.8	10.1±2.2	0.504

Abbreviations: neCRSwNP, non-eosinophilic chronic rhinosinusitis with nasal polyps; eCRSwNP, eosinophilic chronic rhinosinusitis with nasal polyps; HC, healthy control; BMI, body mass index; VAS, visual analogue scale; NA, not applicable.

Figure 1 CRSwNP tissue specimens H&E staining and tissue eosinophil counts in HPF. (A and B) Typical histological figures of neCRSwNP and eCRSwNP. (C and D) The eosinophils counts and percentages were significantly higher in eCRSwNP patients than neCRSwNP. ***p < 0.001.

Notes: All CRSwNP tissue specimens from nasal polyp tissue of undergoing functional endoscopic sinus surgery. Arrows point to eosinophils in the image.

Abbreviations: eCRSwNP, eosinophilic chronic rhinosinusitis with nasal polyps; neCRSwNP, non-eosinophilic chronic rhinosinusitis with nasal polyps; HPF, high-power field.

Table 2 Correlation Between Serum YKL-40 and Clinical Variables in CRSwNP Patients

Variables	r	P
Age, years	0.039	0.729
BMI, kg/m^2	−0.084	0.458
Blood eosinophil counts (10^9/L)	0.200	0.075
Blood eosinophil percentage (%)	0.221	0.048
Preoperative VAS score	0.069	0.541
Preoperative Lund–Mackay score	0.011	0.929
Tissue eosinophil counts (n/HPF)	0.423	0.005
Tissue eosinophil percentages (%)	0.686	<0.001

Abbreviations: CRSwNP, chronic rhinosinusitis with nasal polyps; BMI, body mass index; VAS, visual analogue scale; HPF, high-power field.

Table 3 Logistic Regression Analysis of Factors Associated with CRSwNP Phenotypes

Variables	OR	95% CI	P
Serum YKL-40 level (ng/mL)	3.019	1.623–6.023	0.008
Allergic rhinitis (yes/no), n	1.532	1.136–2.264	0.026
Asthma (yes/no), n	1.721	0.896–2.532	0.239
Blood eosinophil counts (10^9/L)	2.134	1.417–3.568	0.030
Blood eosinophil percentage (%)	2.537	1.312–5.072	0.004

Abbreviations: CRSwNP, chronic rhinosinusitis with nasal polyps; OR, odds ratio; CI, confidence interval.

Table 4 ROC Analysis Results of Different Variables for Distinguishing CRSwNP Phenotypes

Variables	AUC (95% CI)	P	Cutoff Value	Sensitivity	Specificity
Serum YKL-40 level (ng/mL)	0.790 (0.692–0.889)	<0.001	30.8	0.639	0.831
Blood eosinophil counts (10^9/L)	0.603 (0.477–0.728)	0.115	0.3	0.540	0.589
Blood eosinophil percentage (%)	0.743 (0.634–0.852)	<0.001	2.7	0.791	0.647

Abbreviations: ROC, receiver operating characteristics; CRSwNP, chronic rhinosinusitis with nasal polyps; AUC, area under the curve; CI, confidence interval.

Figure 2 Comparison of serum YKL-40 level between HC and CRSwNP. (A) Serum YKL-40 levels were elevated in the CRSwNP than HC. (B) Serum YKL-40 levels were significantly increased in the eCRSwNP than HC and neCRSwNP. *p < 0.05; **p < 0.01.

Abbreviations: HC, health control; CRSwNP, chronic rhinosinusitis with nasal polyps; eCRSwNP, eosinophilic chronic rhinosinusitis with nasal polyps; neCRSwNP, non-eosinophilic chronic rhinosinusitis with nasal polyps.

Figure 3 Receiver operating characteristics curves of serum YKL-40 level (red line), blood eosinophil counts (purple line), and blood eosinophil percentage (green line).

Table 5 Demographic Characteristics Between Primary and Recurrent CRSwNP Patients

Variables	Primary CRSwNP (n=80)	Recurrent CRSwNP (n=40)	P
Age, years	43.4±9.6	47.1±12.3	0.075
Gender (male/female)	48/32	23/17	0.845
Smoking (yes/no), n	22/58	12/28	0.831
Drinking (yes/no), n	8/72	3/37	0.750
BMI, kg/m^2	23.4±1.7	22.9±1.6	0.108
Allergic rhinitis (yes/no), n	15/65	16/24	0.016
Asthma (yes/no), n	8/72	8/32	0.157
Blood eosinophil counts (10^9/L)	0.3±0.1	0.4±0.1	<0.001
Blood eosinophil percentage (%)	2.9±1.0	4.2±1.2	<0.001
Preoperative VAS score	5.8±1.7	6.0±1.9	0.655
Preoperative Lund–Mackay score	9.8±2.2	9.4±2.2	0.305
Tissue eosinophil counts (n/HPF)	28.9±22.1	52.0±27.0	<0.001
Tissue eosinophil percentage (%)	12.2±7.6	21.7±10.7	<0.001
neCRSwNP/eCRSwNP	43/37	11/29	0.007

Abbreviations: neCRSwNP, non-eosinophilic chronic rhinosinusitis with nasal polyps; eCRSwNP, eosinophilic chronic rhinosinusitis with nasal polyps; BMI, body mass index; VAS, visual analogue scale; HPF, high-power field.

Table 6 Logistic Regression Analysis of Factors Affected the Rate of Recurrence in CRSwNP Patients

Variables	OR	95% CI	P
Allergic rhinitis (yes/no), n	2.101	0.977–4.012	0.253
Blood eosinophil counts (10^9/L)	1.845	0.963–3.154	0.652
Blood eosinophil percentage (%)	2.012	1.301–5.016	0.009
Tissue eosinophil counts (n/HPF)	2.414	1.403–5.123	0.024
Tissue eosinophil percentage (%)	3.012	1.587–6.993	0.002
neCRSwNP/eCRSwNP	1.687	1.025–3.874	0.033
Serum YKL-40 level (ng/mL)	2.976	1.353–6.012	<0.001

Abbreviations: CRSwNP, chronic rhinosinusitis with nasal polyps; neCRSwNP, non-eosinophilic chronic rhinosinusitis with nasal polyps; eCRSwNP, eosinophilic chronic rhinosinusitis with nasal polyps; OR, odds ratio; CI, confidence interval; HPF, high-power field.

Table 7 ROC Analysis Results of Indicators for Predicting the Recurrence of CRSwNP

Variables	AUC (95% CI)	P	Cutoff Value	Sensitivity	Specificity
Tissue eosinophil counts (n/HPF)	0.709 (0.640–0.818)	<0.001	35.0	0.562	0.841
Blood eosinophil percentage (%)	0.619 (0.506–0.732)	0.034	0.4	0.611	0.764
Serum YKL-40 level (ng/mL)	0.813 (0.750–0.895)	<0.001	33.2	0.772	0.831
Tissue eosinophil percentage (%)	0.802 (0.717–0.888)	<0.001	13.7	0.547	0.822

Abbreviations: ROC, receiver operating characteristics; CRSwNP, chronic rhinosinusitis with nasal polyps; AUC, area under the curve; CI, confidence interval; HPF, high-power field.

Figure 4 Comparison of serum YKL-40 level between CRSwNP and recurrent CRSwNP. (A) Serum YKL-40 levels were distinctly higher in the rCRSwNP than CRSwNP. (B) Serum YKL-40 levels were significantly increased in recurrent eCRSwNP compared with primary neCRSwNP, primary eCRSwNP, and recurrent neCRSwNP. *p < 0.05; **p < 0.01. ns, not significant.

Abbreviations: CRSwNP, chronic rhinosinusitis with nasal polyps; rCRSwNP, recurrent chronic rhinosinusitis with nasal polyps; eCRSwNP, eosinophilic chronic rhinosinusitis with nasal polyps; neCRSwNP, non-eosinophilic chronic rhinosinusitis with nasal polyps.

Figure 5 Receiver operating characteristics curves of serum YKL-40 level (green line), tissue eosinophil counts (blue line), blood eosinophil percentage (red line), and tissue eosinophil percentage (orange line).

Figure 6 The mRNA expression levels of YKL-40 in the tissue of CRSwNP patient and health controls. The mRNA expression levels of YKL-40 among healthy controls, eCRSwNP and neCRSwNP patients. (A) The mRNA expression levels of YKL-40 in primary CRSwNP and recurrent CRSwNP patients. (B) *p < 0.05, **p < 0.01, ****p < 0.0001. ns, not significant.

Abbreviations: HC, health control; CRSwNP, chronic rhinosinusitis with nasal polyps; eCRSwNP, eosinophilic chronic rhinosinusitis with nasal polyps; neCRSwNP, non-eosinophilic chronic rhinosinusitis with nasal polyps.

Figure 7 Immunohistochemical staining of YKL-40 in HC, eCRSwNP, neCRSwNP and rCRSwNP patients. (×200 and ×400 magnification). (A and B) HC group. (C and D) neCRSwNP group. (E and F) eCRSwNP group. (G and H) rCRSwNP group.

Notes: HC group specimen from the middle turbinate of same region. Each CRSwNP groups specimens from the nasal polyps of undergoing functional endoscopic sinus surgery.

Abbreviations: HC, healthy control; CRSwNP, chronic rhinosinusitis with nasal polyps; neCRSwNP, non-eosinophilic chronic rhinosinusitis with nasal polyps; eCRSwNP, eosinophilic chronic rhinosinusitis with nasal polyps; rCRSwNP, recurrent chronic rhinosinusitis with nasal polyps.