Background: A hallmark of eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is mucosal eosinophil-predominant inflammation. Nasal nitric oxide (nNO) is a known biomarker of eosinophilic inflammation in the upper airway. However, the utility of nNO measurement in the upper airway remains controversial. The present study aimed to compare the use of other clinical parameters with nNO to prediagnose patients with eCRSwNP from Central China. Methods: From June 2019 to December 2019, 70 patients with CRSwNP undergoing endoscopic sinus surgery and 30 healthy subjects were enrolled. nNO measurements were performed in all of these subjects. Computed tomography scans, full blood count with differential analysis, and determination of total immunoglobulin E (total IgE) and plasma cytokines were performed before surgery. Receiver operating characteristic curves and logistic regression analysis were used to assess the predictive potential of the clinical parameters. Results: We recruited 24 patients with eCRSwNP and 46 with noneosinophilic CRSwNP (non-eCRSwNP). In patients with eCRSwNP, nNO levels were significantly higher than those in patients with non-eCRSwNP (p < 0.0001). Blood eosinophil percentages and counts, total IgE, and CT-derived ethmoid sinus and maxillary sinus ratio (E/M ratio) were all significantly higher compared with those in patients with non-eCRSwNP (p < 0.05). To diagnose eCRSwNP, the highest area under the curve (0.803) was determined for nNO. At a cutoff of >329 parts per billion (ppb), the sensitivity was 83.30% and the specificity was 71.70%. However, the levels of plasma cytokines Th1/Th2 were not significantly different between the histological types of CRSwNP (p > 0.05). Conclusion: Measurement of nNO is useful for the early diagnosis of eCRSwNP.

1.
Saito
DM
,
Innes
AL
,
Pletcher
SD
.
Rheologic properties of sinonasal mucus in patients with chronic sinusitis
.
Am J Rhinol Allergy
.
2010 Jan–Feb
;
24
(
1
):
1
5
.
2.
Lou
H
,
Zhang
N
,
Bachert
C
,
Zhang
L
.
Highlights of eosinophilic chronic rhinosinusitis with nasal polyps in definition, prognosis, and advancement
.
Int Forum Allergy Rhinol
.
2018 Nov
;
8
(
11
):
1218
25
.
3.
Wang
X
,
Zhang
N
,
Bo
M
,
Holtappels
G
,
Zheng
M
,
Lou
H
, et al
Diversity of TH cytokine profiles in patients with chronic rhinosinusitis: a multicenter study in Europe, Asia, and Oceania
.
J Allergy Clin Immunol
.
2016 Nov
;
138
(
5
):
1344
53
.
4.
Van Zele
T
,
Claeys
S
,
Gevaert
P
,
Van Maele
G
,
Holtappels
G
,
Van Cauwenberge
P
, et al
Differentiation of chronic sinus diseases by measurement of inflammatory mediators
.
Allergy
.
2006 Nov
;
61
(
11
):
1280
9
.
5.
Zhang
N
,
Van Zele
T
,
Perez-Novo
C
,
Van Bruaene
N
,
Holtappels
G
,
DeRuyck
N
, et al
Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease
.
J Allergy Clin Immunol
.
2008 Nov
;
122
(
5
):
961
8
.
6.
Ikeda
K
,
Shiozawa
A
,
Ono
N
,
Kusunoki
T
,
Hirotsu
M
,
Homma
H
, et al
Subclassification of chronic rhinosinusitis with nasal polyp based on eosinophil and neutrophil
.
Laryngoscope
.
2013 Nov
;
123
(
11
):
e1
9
.
7.
Akdis
CA
,
Bachert
C
,
Cingi
C
,
Dykewicz
MS
,
Hellings
PW
,
Naclerio
RM
, et al
Endotypes and phenotypes of chronic rhinosinusitis: a PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology
.
J Allergy Clin Immunol
.
2013 Jun
;
131
(
6
):
1479
90
.
8.
Gurrola
J
 2nd
,
Borish
L
.
Chronic rhinosinusitis: endotypes, biomarkers, and treatment response
.
J Allergy Clin Immunol
.
2017 Dec
;
140
(
6
):
1499
508
.
9.
Haruna
S
,
Shimada
C
,
Ozawa
M
,
Fukami
S
,
Moriyama
H
.
A study of poor responders for long-term, low-dose macrolide administration for chronic sinusitis
.
Rhinology
.
2009 Mar
;
47
(
1
):
66
71
.
10.
Hauser
LJ
,
Chandra
RK
,
Li
P
,
Turner
JH
.
Role of tissue eosinophils in chronic rhinosinusitis-associated olfactory loss
.
Int Forum Allergy Rhinol
.
2017 Oct
;
7
(
10
):
957
62
.
11.
Vlaminck
S
,
Vauterin
T
,
Hellings
PW
,
Jorissen
M
,
Acke
F
,
Van Cauwenberge
P
, et al
The importance of local eosinophilia in the surgical outcome of chronic rhinosinusitis: a 3-year prospective observational study
.
Am J Rhinol Allergy
.
2014 May–Jun
;
28
(
3
):
260
4
.
12.
Kim
SJ
,
Lee
KH
,
Kim
SW
,
Cho
JS
,
Park
YK
,
Shin
SY
.
Changes in histological features of nasal polyps in a Korean population over a 17-year period
.
Otolaryngol Head Neck Surg
.
2013 Sep
;
149
(
3
):
431
7
.
13.
Katotomichelakis
M
,
Tantilipikorn
P
,
Holtappels
G
,
De Ruyck
N
,
Feng
L
,
Van Zele
T
, et al
Inflammatory patterns in upper airway disease in the same geographical area may change over time
.
Am J Rhinol Allergy
.
2013 Sep–Oct
;
27
(
5
):
354
60
.
14.
Wang
W
,
Gao
Y
,
Zhu
Z
,
Zha
Y
,
Wang
X
,
Qi
F
, et al
Changes in the clinical and histological characteristics of Chinese chronic rhinosinusitis with nasal polyps over 11 years
.
Int Forum Allergy Rhinol
.
2019 Feb
;
9
(
2
):
149
57
.
15.
Jiang
WX
,
Cao
PP
,
Li
ZY
,
Zhai
GT
,
Liao
B
,
Lu
X
, et al
A retrospective study of changes of histopathology of nasal polyps in adult Chinese in central China
.
Rhinology
.
2019 Aug 1
;
57
(
4
):
261
7
.
16.
Naraghi
M
,
Deroee
AF
,
Ebrahimkhani
M
,
Kiani
S
,
Dehpour
A
.
Nitric oxide: a new concept in chronic sinusitis pathogenesis
.
Am J Otolaryngol
.
2007 Sep–Oct
;
28
(
5
):
334
7
.
17.
Ferraro
VA
,
Zanconato
S
,
Baraldi
E
,
Carraro
S
.
Nitric oxide and biological mediators in pediatric chronic rhinosinusitis and asthma
.
J Clin Med
.
2019 Oct
;
8
(
11
):
1783
.
18.
Deroee
AF
,
Naraghi
M
,
Sontou
AF
,
Ebrahimkhani
MR
,
Dehpour
AR
.
Nitric oxide metabolites as biomarkers for follow-up after chronic rhinosinusitis surgery
.
Am J Rhinol Allergy
.
2009 Mar–Apr
;
23
(
2
):
159
61
.
19.
Ricciardolo
FL
,
Sorbello
V
,
Ciprandi
G
.
FeNO as biomarker for asthma phenotyping and management
.
Allergy Asthma Proc
.
2015 Jan–Feb
;
36
(
1
):
e1
8
.
20.
Ragab
SM
,
Lund
VJ
,
Saleh
HA
,
Scadding
G
.
Nasal nitric oxide in objective evaluation of chronic rhinosinusitis therapy
.
Allergy
.
2006 Jun
;
61
(
6
):
717
24
.
21.
Shapiro
AJ
,
Josephson
M
,
Rosenfeld
M
,
Yilmaz
O
,
Davis
SD
,
Polineni
D
, et al
Accuracy of nasal nitric oxide measurement as a diagnostic test for primary ciliary dyskinesia. A systematic review and meta-analysis
.
Ann Am Thorac Soc
.
2017 Jul
;
14
(
7
):
1184
96
.
22.
Fu
CH
,
Huang
CC
,
Chen
YW
,
Chang
PH
,
Lee
TJ
.
Nasal nitric oxide in relation to quality-of-life improvements after endoscopic sinus surgery
.
Am J Rhinol Allergy
.
2015 Nov–Dec
;
29
(
6
):
e187
91
.
23.
Fokkens
WJ
,
Lund
VJ
,
Mullol
J
,
Bachert
C
,
Alobid
I
,
Baroody
F
, et al
European position paper on rhinosinusitis and nasal polyps 2012
.
Rhinol Suppl
.
2012 Mar
;
23
:
3
.
24.
Dweik
RA
,
Boggs
PB
,
Erzurum
SC
,
Irvin
CG
,
Leigh
MW
,
Lundberg
JO
, et al
An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications
.
Am J Respir Crit Care Med
.
2011 Sep
;
184
(
5
):
602
15
.
25.
Cao
PP
,
Li
HB
,
Wang
BF
,
Wang
SB
,
You
XJ
,
Cui
YH
, et al
Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese
.
J Allergy Clin Immunol
.
2009 Sep
;
124
(
3
):
478
84
.
26.
Czerny
MS
,
Namin
A
,
Gratton
MA
,
Antisdel
JL
.
Histopathological and clinical analysis of chronic rhinosinusitis by subtype
.
Int Forum Allergy Rhinol
.
2014 Jun
;
4
(
6
):
463
9
.
27.
Rimmer
J
,
Hellings
P
,
Lund
VJ
,
Alobid
I
,
Beale
T
,
Dassi
C
, et al
European position paper on diagnostic tools in rhinology
.
Rhinology
.
2019 Jul 25
;
57
(
Suppl S28
):
1
41
.
28.
Frendø
M
,
Håkansson
K
,
Schwer
S
,
Ravn
AT
,
Meteran
H
,
Porsbjerg
C
, et al
Exhaled and nasal nitric oxide in chronic rhinosinusitis patients with nasal polyps in primary care
.
Rhinology
.
2018 Mar 1
;
56
(
1
):
59
64
.
29.
Ambrosino
P
,
Molino
A
,
Spedicato
GA
,
Parrella
P
,
Formisano
R
,
Motta
A
, et al
Nasal nitric oxide in chronic rhinosinusitis with or without nasal polyps: a systematic review with meta-analysis
.
J Clin Med
.
2020 Jan 11
;
9
(
1
):
200
.
30.
Colantonio
D
,
Brouillette
L
,
Parikh
A
,
Scadding
GK
.
Paradoxical low nasal nitric oxide in nasal polyposis
.
Clin Exp Allergy
.
2002 May
;
32
(
5
):
698
701
.
31.
Jonstam
K
,
Swanson
BN
,
Mannent
LP
,
Cardell
LO
,
Tian
N
,
Wang
Y
, et al
Dupilumab reduces local type 2 pro-inflammatory biomarkers in chronic rhinosinusitis with nasal polyposis
.
Allergy
.
2019 Apr
;
74
(
4
):
743
52
.
32.
Mahr
TA
,
Malka
J
,
Spahn
JD
.
Inflammometry in pediatric asthma: a review of fractional exhaled nitric oxide in clinical practice
.
Allergy Asthma Proc
.
2013 May–Jun
;
34
(
3
):
210
9
.
33.
Takeno
S
,
Taruya
T
,
Ueda
T
,
Noda
N
,
Hirakawa
K
.
Increased exhaled nitric oxide and its oxidation metabolism in eosinophilic chronic rhinosinusitis
.
Auris Nasus Larynx
.
2013 Oct
;
40
(
5
):
458
64
.
34.
Yoshida
K
,
Takabayashi
T
,
Imoto
Y
,
Sakashita
M
,
Narita
N
,
Fujieda
S
.
Reduced nasal nitric oxide levels in patients with eosinophilic chronic rhinosinusitis
.
Allergol Int
.
2019 Apr
;
68
(
2
):
225
32
.
35.
Kim
JW
,
Hong
SL
,
Kim
YK
,
Lee
CH
,
Min
YG
,
Rhee
CS
.
Histological and immunological features of non-eosinophilic nasal polyps
.
Otolaryngol Head Neck Surg
.
2007 Dec
;
137
(
6
):
925
30
.
36.
Ishitoya
J
,
Sakuma
Y
,
Tsukuda
M
.
Eosinophilic chronic rhinosinusitis in Japan
.
Allergol Int
.
2010 Sep
;
59
(
3
):
239
45
.
37.
Kountakis
SE
,
Arango
P
,
Bradley
D
,
Wade
ZK
,
Borish
L
.
Molecular and cellular staging for the severity of chronic rhinosinusitis
.
Laryngoscope
.
2004 Nov
;
114
(
11
):
1895
905
.
38.
Hu
Y
,
Cao
PP
,
Liang
GT
,
Cui
YH
,
Liu
Z
.
Diagnostic significance of blood eosinophil count in eosinophilic chronic rhinosinusitis with nasal polyps in Chinese adults
.
Laryngoscope
.
2012 Mar
;
122
(
3
):
498
503
.
39.
Lou
H
,
Meng
Y
,
Piao
Y
,
Wang
C
,
Zhang
L
,
Bachert
C
.
Predictive significance of tissue eosinophilia for nasal polyp recurrence in the Chinese population
.
Am J Rhinol Allergy
.
2015 Sep–Oct
;
29
(
5
):
350
6
.
40.
Kambara
R
,
Minami
T
,
Akazawa
H
,
Tsuji
F
,
Sasaki
T
,
Inohara
H
, et al
Lower airway inflammation in eosinophilic chronic rhinosinusitis as determined by exhaled nitric oxide
.
Int Arch Allergy Immunol
.
2017
;
173
(
4
):
225
32
.
41.
Ho
J
,
Hamizan
AW
,
Alvarado
R
,
Rimmer
J
,
Sewell
WA
,
Harvey
RJ
.
Systemic predictors of eosinophilic chronic rhinosinusitis
.
Am J Rhinol Allergy
.
2018 Jul
;
32
(
4
):
252
7
.
42.
Wei
B
,
Liu
F
,
Zhang
J
,
Liu
Y
,
Du
J
,
Liu
S
, et al
Multivariate analysis of inflammatory endotypes in recurrent nasal polyposis in a Chinese population
.
Rhinology
.
2018 Sep 1
;
56
(
3
):
216
26
.
43.
Wang
ET
,
Zheng
Y
,
Liu
PF
,
Guo
LJ
.
Eosinophilic chronic rhinosinusitis in East Asians
.
World J Clin Cases
.
2014 Dec 16
;
2
(
12
):
873
82
.
44.
Zuo
L
,
Koozechian
MS
,
Chen
LL
.
Characterization of reactive nitrogen species in allergic asthma
.
Ann Allergy Asthma Immunol
.
2014 Jan
;
112
(
1
):
18
22
.
45.
Meng
Y
,
Lou
H
,
Wang
C
,
Zhang
L
.
Predictive significance of computed tomography in eosinophilic chronic rhinosinusitis with nasal polyps
.
Int Forum Allergy Rhinol
.
2016 Aug
;
6
(
8
):
812
9
.
46.
Sakuma
Y
,
Ishitoya
J
,
Komatsu
M
,
Shiono
O
,
Hirama
M
,
Yamashita
Y
, et al
New clinical diagnostic criteria for eosinophilic chronic rhinosinusitis
.
Auris Nasus Larynx
.
2011 Oct
;
38
(
5
):
583
8
.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.