La yngoscope In es iga i e O ola yngology
V
C2016 The Au ho s La yngoscope In es iga i e O ola yngology
published by Wiley Pe iodicals, Inc. on behal o The T iological Socie y
Fac o s A ec ing Re ision Ra e o Ch onic Rhinosinusi is
Anni Koskinen, MD; Riikka Salo, BDen ; Heini Huh ala, MSci; Jy i Mylle , MD, PhD;
Ma kus Rau iainen, MD, PhD; Janne K€
a€
a i€
ainen, MD, PhD; Ma i Pen il€
a, MD, PhD;
Ris o Renkonen, MD, PhD; Hannu Rai iola, MD, PhD; Mika M€
akel€
a, MD, PhD;
Sanna Toppila-Salmi, MD, PhD
Objec i e: Ch onic hinosinusi is (CRS) is a a iable mul i ac o ial disease. I can be di ided in o o ms wi h nasal pol-
yps (CRSwNP) and wi hou (CRSsNP). Sinus and/o nasal polypec omy su ge y a e conside ed i maximal conse a i e ea -
men is insu icien . The p edic i e ac o s o he need o e ision su ge y comp ise mos ly he CRSwNP pheno ype and a e
no ully unde s ood.
S udy Design: The aim o his ollow-up s udy was o e alua e he ac o s associa ed wi h he e ision su ge y a e in
CRS pa ien s wi h a iable ex en o disease.
Me hods: Da a o CRS pa ien s (N 5178) unde going sinus su ge y and/o nasal polypec omy in 2001 o 2010 we e
used. Pa ien cha ac e is ics and ollow-up da a we e collec ed om pa ien eco ds and ques ionnai es. Associa ions we e
analyzed by Fishe ’s exac , Mann Whi ney U, and he Kaplan-Meie me hod wi h log- ank es . Unadjus ed Cox’s p opo ional
haza d models we e used o 12 a iables and we e i ed o he need o e ision sinus su ge y and/o nasal polypec omy
du ing ollow-up o in a e age 9 yea s.
Resul s: The p opo ion o CRS pa ien s who had unde gone e ision in 5 yea s was 9.6%. A e adjus men , he ollow-
ing ac o s associa ed signi ican ly wi h he need o ecu en CRS su ge y: alle gic hini is, co icos e oid ea men , p e i-
ous su ge y o CRS, and ecu en NP.
Conclusion: Inc eased isk o p og essi e CRS pheno ypes wi h he need o e ision su ge y would pu a i ely be ecog-
nized by ela i ely simple clinical ques ions. Fu he s udies wi h inc eased sample size a e needed o e alua e whe he hese
p edic i e ac o s would be ele an o de eloping be e de ec ion and managemen o p og essi e CRS.
Key Wo ds: An ochoanal polyp, aspi in-exace ba ed espi a o y disease, aspi in in ole ance, in lamma ion, nasal polyp,
sinusi is, sinus su ge y, ecu ence, e ision su ge y.
Le el o E idence: 2b.
INTRODUCTION
Ch onic hinosinusi is (CRS) is a he e ogeneous
g oup o in lamma o y diseases o he nose and pa a-
nasal sinuses las ing o a leas 12 weeks
1
; i is one o
he mos common ch onic adul heal h p oblems in he
Wes e n wo ld. A Eu opean s udy es ima ed he p e a-
lence o ch onic hinosinusi is (CRS) a 11%, al hough a
p e alence o 6% o 7% has been obse ed in s udies
wi h physician-led diagnosis o CRS.
2–5
Ch onic hinosi-
nusi is has a se e e impac on quali y o li e ha is com-
pa able wi h o he ch onic diseases such as as hma,
ch onic obs uc i e pulmona y disease, and diabe es.
1
The economic bu den caused by CRS is signi ican and
ela es la gely o loss o p oduc i i y, inc eased doc o ’s
appoin men s, and medical expenses. In Uni ed S a es,
he CRS- ela ed heal hca e cos s a e es ima ed o be
$6.9 o $9.9 billion dolla s (USD) pe yea .
6
The p edisposing ac o s o CRS include gene ic ac-
o s, ana omic abno mali ies, ai bo ne i i an s/alle gens/
mic obes, and hos immuni y.
7
Ch onic hinosinusi is
wi h nasal polyps (CRSwNP) and wi hou (CRSsNP) a e
conside ed o be pheno ypes o CRS wi h possibly di e -
en e iologies and pa homechanisms.
1
Howe e , hey may
also be in e p e ed as di e en deg ees o in lamma ion.
1
CRSwNP a ec s be ween 1% and 4% o he gene al popu-
la ion.
1
Aspi in-exace ba ed espi a o y disease (AERD)
F om he Haa man Ins i u e, Uni e si y o Helsinki (A.K., R.S.,
R.R., S.T-S.); he Depa men o O o hinola yngology (A.K.); he Depa -
men o Alle gy (M.M., S.T-S.), Uni e si y o Helsinki and Helsinki Uni e -
si y Hospi al; he Te eys alo Heal hca e OYJ o Finland (M.P.); he
HUSLAB (R.R.), Helsinki; he School o Heal h Sciences, (H.H.); he
Depa men o O o hinola yngology (M.R., M.P.), Uni e si y o Tampe e;
he Depa men o O o hinola yngology, Tampe e Uni e si y Hospi al
(M.R., J.K.); he Depa men o O o hinola yngology, Tampe e Ci y Hospi-
al (H.R.), Tampe e; and he Depa men o O o hinola yngology, P€
aij€
a -
H€
ame Cen al Hospi al (J.M.) Lah i, Finland.
Edi o ’s No e: This Manusc ip was accep ed o publica ion 5
June 2016.
This is an open access a icle unde he e ms o he C ea i e
Commons A ibu ion-NonComme cial-NoDe i s License, which pe mi s
use and dis ibu ion in any medium, p o ided he o iginal wo k is p op-
e ly ci ed, he use is non-comme cial and no modi ica ions o adap a ions
a e made.
Funding: The s udy was suppo ed in pa by he Compe i i e
Resea ch Funding o he Tampe e Medical Resea ch Fund o Tampe e
Uni e si y Hospi al, and in pa by esea ch g an s om he Finnish
Medical Founda ion, Finnish Associa ion o O o hinola yngology and
Head and Neck Su ge y, Finnish Socie y o Alle gology and Immunology,
Jane and Aa os E kko Founda ion, V€
ain€
o and Laina Ki i Founda ion,
and Y j€
o Jahnsson Founda ion.
M. P. is a s ockholde in a medical ins umen company (L d, Tam-
pe e, Finland) ha is ma ke ing bo h balloon sinuplas y and ESS su gi-
cal ins umen s. The au ho s ha e no o he unding, inancial
ela ionships, o con lic s o in e es o disclose.
Send co espondence o Sanna Toppila-Salmi, MD, PhD, Haa -
man Ins i u e, PO BOX 21 (Haa maninka u 3), 00014 Uni e si y o
Helsinki, Helsinki, Finland. E-mail: sanna.salmi@helsinki. i
DOI: 10.1002/lio2.27
La yngoscope In es iga i e O ola yngology 1: Augus 2016 Koskinen e al.: Fac o s A ec ing Re ision Ra e o CRS
96
has been epo ed in 8% o 26% o pa ien s wi h
CRSwNP
8
; i is cha ac e ized by se e e eosinophilic
hype plas ic in lamma ion o all sinuses and nasal pas-
sages, as well as o he lowe ai ways.
9
Endoscopic sinus su ge y (ESS) has been he mos
common ype o su ge y o hinosinusi is o hose wi h
ailed maximal medical ea men s.
1
The a ia ion in
using ope a i e managemen in CRS migh e lec a num-
be o ac o s, including bo h unde u iliza ion and o e u-
iliza ion o su ge y, a lack o guidelines, and a lack o
e idence in well-cons uc ed andomized con olled ials
(RCTs) .
2
The Coch ane collabo a ion s a ed in 2006 ha
ESS o e s no addi ional bene i in elie ing symp oms o
CRS compa ed o medical ea men .
10
A ha ime, only
six andomized con olled ials we e a ailable. Al hough
le el 1 e idence is lacking, ecen s udies e alua ing he
symp oma ic and economic bene i s o su gical in e en-
ion in CRS a o su gical in e en ion o e ongoing med-
ical he apy.
2,11,12
S udies also sugges ha pa ien s wi h
p olonged and ch onic disease migh bene i mo e om
su ge y han con inued medical he apy.
6
Endoscopic sinus su ge y usually has high ini ial
success a e.
1
Published success a es o ESS ange
om 76% o 98%.
13
Common ailu e ac o s associa ed
wi h ESS include inapp op ia e su gical echnique, poo
ope a i e ield o isualiza ion, and inadequa e pos ope -
a i e ca e.
13
Re ision ESS is likely o pose mo e su gical
isks han p ima y ESS because majo complica ion
a es app oxima e 1%.
14,15
Re ision a es ange om 3%
o 20%, depending mos ly on he popula ion and ollow-
up ime.
14,15
Acco ding o a la ge p ospec i e coho
s udy, app oxima ely 20% o pa ien s esponded unsa is-
ac o ily o su ge y and equi ed e ision du ing he 5-
yea ollow-up.
15
In his s udy, 20.6% o he pa ien s
wi h polyps had e ision su ge y in he p e ious 5 yea s
compa ed o 15.5% o he pa ien s wi h CRS alone.
15
A ew pa ien s ha e p og essi e and ecu en o ms
o CRS, which is challenging o pa ien s and clinicians.
16
P e ious s udies ha e mos ly been pe o med in CRSwNP
pheno ype and ha e shown ha he ollowing ac o s
associa e wi h he equen e isions o CRS: male gen-
de , young adul s, smoking, occupa ional exposu e, adio-
logical in lamma o y indings in on al sinus(es),
p esence o nasal polyps, as hma, and AERD.
16–22
The e
is a need o e alua e ac o s associa ed wi h he e ision
a e in se e al ypes o CRS. The pu pose o his s udy is
o iden i y he clinical ac o s ha in luence he numbe
and ime o e ision sinus su ge y and/o nasal polypec-
omy in he e ogeneous g oup o CRS pa ien s.
MATERIALS AND METHODS
Pa ien s
This s udy was pe o med a he Depa men s o O o hi-
nola yngology, Tampe e Uni e si y Hospi al, P€
aij€
a -H€
ame Cen-
al Hospi al, Mikkeli Cen al Hospi al, Tampe e Ci y Hospi al,
and Haa man Ins i u e, Uni e si y o Helsinki, Finland. The
s udy p o ocol was app o ed by he E hical Commi ee o Pi -
kanmaa Hospi al Dis ic and he Adminis a ion o he Hospi-
al. W i en in o med consen was no equi ed o he
e ospec i e s udy popula ions (II–III) and o he collec ion o
ollow-up da a om pa ien eco ds o s udy I popula ion. The
s udy popula ion was composed o di e en pheno ypes o CRS
pa ien s who had unde gone o a iable ex en sinus su ge y
and/o polypec omy in 2001 o 2010 (N5205). The ollow-up
da a was a ailable om he hospi al’s pa ien eco ds o ques-
ionnai es om a o al o 178 (87%) CRS pa ien s. The CRS
pa ien s we e om h ee p eexis ing s udies.
23–26
The i s s udy
da a was collec ed om an ini ial s udy, which was a p ospec i e
ollow-up s udy ha included wo se s o pa ien s who unde wen
maxilla y sinus su ge y be ween 2001 o 2002. O hose, 32 CRS
pa ien s (16 p e iously ope a ed) unde wen maxilla y sinus
su ge y 6e hmoidec omy 6nasal polypec omy, and 25 non-
p e iously ope a ed CRSsNP pa ien s unde wen simple
uncinec omy-only on one side and simple uncinec omy wi h mid-
dle mea al an os omy on he o he side.
25,26
W i en in o med
consen om he ini ial i s p ospec i e s udy pa ien s was
ob ained. The second s udy was a e ospec i e ollow-up s udy
o 63 CRSwNP pa ien s (16 p e iously ope a ed) who unde wen
nasal polypec omy 6sinus su ge y be ween 2005 o 2006.
23
Eigh
o hese CRSwNP pa ien s had an ochoanal polyps (ACP) and
we e a pa o a andom sample o ou hospi al’s nasal polyp
cases. The hi d s udy was a e ospec i e ollow-up s udy o 58
nonope a ed CRSsNP pa ien s. O hese, 28 had unde gone sim-
ple maxilla y balloon sinuplas y and 30 simple middle-mea al
an os omy be ween 2008 o 2010.
24
Diagnosis o CRSsNP,
CRSwNP, o ACP was based on he c i e ia o he Eu opean posi-
ion pape on hinosinusi is and nasal polyps (EPOS) o symp-
oms, endoscopic, and sinus compu ed omog aphy indings we e
based on he pa ien eco ds.
1
The exclusion c i e ia in all
coho s we e cys ic ib osis and p ima y cilia y dyskinesia.
Da a Collec ion
Pa ien eco ds we e abs ac ed o ime un il e ision su -
ge y and a iables ha could po en ially in luence he need o
e ision su ge y: age; gende ; as hma diagnosis; AERD; AR;
cu en / ecu en NP; p e ious sinus su ge y and/o nasal pol-
ypec omy ope a ion(s); smoking his o y; occupa ional exposu e;
need o egula in anasal co icos e oids; p eope a i ely
adminis e ed pe o al co icos e oid cou se; and he ini ial s udy
ope a ion (only polypec omy, ESS 6polypec omy, only maxilla y
mini-in asi e ESS e.g. uncinec omy-only on one side, only max-
illa y balloon sinuplas y). The numbe o e ision sinus ope a-
ions and/o e ision nasal polypec omies du ing ollow-up we e
calcula ed. Time un il he i s e ision sinus su ge y and/o
nasal polypec omy was de ined a p io i as he ime be ween he
ini ial s udy ope a ion and he i s e ision sinus su ge y and/
o nasal polypec omy du ing ollow-up.
Diagnosis o alle gic hini is was based on subjec -
epo ed doc o -diagnosed AR and/o skin p ick es posi i i y
and epo o ypical symp oms ollowing exposu e o alle gen
o which sensi ized. Diagnosis o as hma was based on a pa ien
eco d o clinical ea u es and diagnos ic pulmona y unc ion
es s, co esponding wi h he Global Ini ia i e o As hma diag-
nos ic c i e ia.
27
Diagnosis o AERD was made on he basis o a
his o y o wheezing o as hma a acks p ecipi a ed by nons e -
oidal an iin lamma o y d ugs. The da a o he p esence o occu-
pa ional exposu e was a ailable only in 107 (60.1%) pa ien s. O
hese, 34 (19.1%) had occupa ional ai way exposu e. The main
subs ances causing job exposu e we e: bioae osols, ag icul u al
o ganic pa icles, wood/ ex ile dus , mi es, molds, lou , and
eac i e chemicals/me alwo k. None o he subjec s had unde -
gone aspi in desensi iza ion, alle gen immuno he apy, o an i
IgE he apy p io o ope a ion o du ing ollow-up.
The in o ma ion o o he gene al diseases han CRS/AR/
as hma was a ailable om 173 pa ien s (97.2%). O hese, he e
La yngoscope In es iga i e O ola yngology 1: Augus 2016 Koskinen e al.: Fac o s A ec ing Re ision Ra e o CRS
97
we e no epo ed o he diseases in 118 (68.2%) pa ien s, and 55
(41.8%) o pa ien s epo ed su e ing om diseases (o he han
CRS/AR/as hma) wi h egula need o medica ions. Twen y-one
(12.1%) pa ien s we e epo ed as ha ing one addi ional disease,
13 (7.5%) as ha ing wo diseases, and 21 (22.2%) as ha ing h ee
o mo e diseases. The mos equen diseases we e (numbe o
pa ien s): hea and ascula diseases (40), nonas hma espi a-
o y diseases (23), obesi y/hype lipidemia/diabe es (15), hy oid
diseases (5), musculoskele al diseases (5), and psychia ic dis-
eases (5).
Da a Analysis
S a is ical analysis was ca ied ou by he IBM SPSS S a-
is ics 23 S a is ical So wa e Package (SPSS Inc., Chicago, IL).
Desc ip i e s a is ics o subjec cha ac e is ics we e p esen ed
in he CRS g oups wi h/wi hou e ision su ge y in 5 yea s.
Fishe ’s exac es (2- ailed) was used o compa e pa ien cha ac-
e is ics. The K uskal-Wallis es and Mann Whi ney U es was
used o s udy he compa ison o he o al Lund-Mackay sco es o
sinus compu ed omog aphy (CT) scans o magne ic esonance
imaging (MRI). The ime pe iods be ween he ini ial s udy ope a-
ion and second su ge ies we e analyzed by he Kaplan-Meie
me hod and compa ed wi h he log- ank es . Su i al was calcu-
la ed om he da e o he ini ial s udy ope a ion o i s ollow-
up e ision sinus su ge y and/o nasal polypec omy/dea h/end o
Ma ch 2015, whiche e came i s . Uni a ia e and mul i a iable
Cox’s p opo ional haza d models o in e al o second su ge y
we e cons uc ed wi h he ollowing p edic o a iables: age; gen-
de ; as hma diagnosis; AERD; AR; cu en / ecu en NP; p e i-
ous sinus su ge y and/o nasal polypec omy ope a ion(s);
smoking his o y; need o egula in anasal co icos e oids; p e-
ope a i ely adminis e ed pe o al co icos e oid cou se; and he
ini ial s udy ope a ion (only polypec omy, ESS6polypec omy,
only maxilla y mini-in asi e ESS e.g. uncinec omy-only on one
side, only maxilla y balloon sinuplas y). The a iables o he
mul i a iable Cox’s p opo ional haza d model we e chosen om
hose ha we e s a is ically signi ican a iables in uni a ia e
Cox’s p opo ional haza d models. S a is ical signi icance was se
a a Ple el o less han 0.05, and all es s we e 2- ailed.
RESULTS
Pa ien Cha ac e is ics
The cha ac e is ics a e shown in Table I. We com-
pa ed he ac o s be ween he g oups wi h/wi hou e i-
sion su ge y in 5 yea s. These pa ien g oups we e
signi ican ly di e en in e ms o he p esence o AR,
need o egula in anasal co icos e oid he apy, and
p e ious sinus su ge y and/o nasal polypec omy (Table
I). P eope a i e sinus CT scans only we e a ailable in 89
(50%) o he pa ien s. O hese, he mean (minimum–
maximum) Lund-Mackay o al sco e o CT scans o MRI
was 7.9 (0–22) in he g oup ha did no unde go e i-
sion su ge y in 5 yea s, and was 8.7 (3–17) in he g oup
ha unde wen e ision su ge y in 5 yea s. This di e -
ence was no s a is ically signi ican (P50.74 by Mann
Whi ney U es ). Sinus su ge y and/o nasal polypec-
omy p io o he ini ial s udy ope a ion had been pe -
o med in 32 (18.0%) pa ien s. O hese, 26 (26.8%) we e
in he CRSwNP g oup and six (7.5%) we e in he
CRSsNP g oup. The di e ence was s a is ically signi i-
can (P50.001, Fishe ’s exac es ).
Re ision Ope a ions Du ing 5-Yea Follow-Up
The e we e 17 (9.6%) CRS pa ien s who had unde -
gone a leas one e ision CRS ope a ion in 5 yea s
(Table I). Du ing he 5-yea ollow-up, he ac o s associ-
a ing signi ican ly wi h he need o e ision sinus su -
ge y and/o nasal polypec omy we e AR, AERD, he
need o egula in anasal co icos e oid ea men , p e-
ope a i e pe o al co icos e oid, p e ious sinus su ge y
and/o nasal polypec omy, and e hmoidec omy pe o med
as pa o cu en su ge y (P<0.02) (Table I) (Fig. 1). In
con as , age, gende , smoking, me hod o he cu en
ope a ion, ecu en NP, and he p esence o as hma o
NP (cu en 6p e ious) did no associa e wi h he e i-
sion du ing ollow-up (P0.05) (Table I). Occupa ional
exposu e, he p esence o gene al diseases, o he num-
be o gene al diseases (o he han CRS/AR/as hma)
we e no associa ed wi h he e ision du ing ollow-up
(P>0.05) .
Re ision Ope a ions Du ing To al Follow-up
Time
The mean (minimum–maximum) o al ollow-up o
all subjec s was 8.7 (1–14) yea s. The e we e eigh
dea hs (6 CRSwNP, 2 CRSsNP) du ing ollow-up ime.
None o he dea hs we e caused by CRS o su ge y o
CRS. None had unde gone e ision o CRS du ing
ollow-up p io o dea h. The o al ollow-up o he
pa ien s who we e ali e un il 2015 was 8.9 (4–14) yea s.
Du ing he o al ollow-up, 17 (9.6%) o he CRS pa ien s
had unde gone one e ision ope a ion; h ee (1.7%)
pa ien s had unde gone wo e isions; and h ee (1.7%)
pa ien s had unde gone h ee e isions. The e ision
ope a ions we e e hmoidec omy (N 514), nasal polypec-
omy (N 57), middle mea al an os omy (N 512), and
on al ecess/sinus su ge y (N 53). Mo eo e , sep o-
plas y was pe o med o ou pa ien s who also unde -
wen CRS su ge y. The e ision ope a ion was mo e
ex ensi e han he p e ious one in 20 (87.0%) o he
cases. The numbe o e ision ope a ions du ing ollow-
up was signi ican ly highe in pa ien s wi h epo ed
AR, AERD, egula need o in anasal co icos e oid, o
wi h p eope a i e pe o al co icos e oid ea men
(P<0.004) (Fig. 1). In con as , he ollowing ac o s did
no associa e wi h he e ision du ing ollow-up: age;
gende ; smoking; occupa ional exposu e; me hod o he
cu en ope a ion; and he p esence o as hma o NP,
he p esence o gene al diseases (o he han CRS/AR/
as hma), o he numbe o gene al diseases (P>0.05,
Fishe ’s exac es ).
Kaplan Meie Su i al Analyses
In he su i al analyses, he mean (minimum–max-
imum) ollow-up ime was 7.9 (1–14) yea s un il he i s
e ision su ge y/dea h/end o Ma ch 2015, whiche e
came i s . The ac o s associa ing signi ican ly wi h he
need o e ision sinus su ge y and/o nasal polypec omy
we e AR, AERD, ecu en NP, he need o egula
in anasal co icos e oid ea men , p eope a i e pe o al
co icos e oid, and p e ious sinus su ge y and/o nasal
La yngoscope In es iga i e O ola yngology 1: Augus 2016 Koskinen e al.: Fac o s A ec ing Re ision Ra e o CRS
98
TABLE I.
Cha ac e is ics o CRS Pa ien s Wi h/Wi hou S a us o Re ision Sinus Su ge y and/o Polypec omy 5 Yea s A e Cu en Ope a ion.
Re ision Sinus Su ge y and/o Polypec omy in
5 Yea s
No (N 5161) Yes (N 517)
N%N%PValue
Gende
Male 79 49.1 7 41.2 .62
Female 82 50.9 10 58.8
Age
<40 yea s 46 28.6 7 41.2 .28
40 yea s 115 71.4 10 58.8
Alle gic hini is
No 101 62.7 4 23.5 .002
Yes 56 34.8 13 76.5
Unknown 4 2.5 0 0
As hma
No 105 65.2 10 58.8 .60
Yes 55 34.2 7 41.2
Unknown 1 0.6 0 0
AERD
No 144 89.4 13 76.5 .12
Yes 17 10.6 4 23.5
Cu en nasal polyps
No 77 47.8 4 23.5 .11
ACP 7 4.3 1 4.9
Con en ional NP 77 47.8 12 70.6
Recu en nasal polyps
No 149 92.5 13 76.5 .05
Yes 12 7.5 4 23.5
P e ious and/o cu en nasal polyps
No o ACP 84 52.2 5 29.4 .06
Yes 77 47.8 12 70.6
Smoke s
No 124 77.0 15 88.2 .53
Yes 34 21.1 2 11.8
Unknown 3 1.9 0 0
Need o egula in anasal co icos e oid
No 93 57.8 2 11.8 <.001
Yes 59 36.6 15 88.2
Unknown 9 5.6 0 0
P eope a i e pe o al co icos e oid
No 148 91.9 12 70.6 .016
Yes 8 5.0 4 23.5
Unknown 5 3.1 1 5.9
P e ious sinus su ge y and/o polypec omy
No 137 85.1 8 47.1 .001
Yes 23 14.3 9 52.9
Unknown 1 0.6 0 0
Cu en sinonasal ope a ion
Only polypec omy 32 19.9 0 0 .13
ESS 6polypec omy 82 50.9 11 64.7
Only maxill. mini-in asi e ESS
1
23 14.3 2 11.8
Only maxill. balloon sinuplas y 24 14.9 4 23.5
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polypec omy (P<0.02) (Fig. 2). Howe e , age, gende ,
smoking, me hod o he cu en ope a ion, o he p es-
ence o as hma o NP did no associa e wi h he e ision
du ing ollow-up (P>0.05) (Table II). The p esence o
occupa ional exposu e o he p esence o o he gene al
diseases han CRS/AR/as hma did no associa e wi h he
need o e ision su ge y (P50.90, P50.27, espec-
i ely, by he log- ank es ).
Cox Reg ession Analyses
Cox’s p opo ional haza ds analysis was conduc ed
o de e mine which ac o s we e p edic i e o su ge y
ecu ence. O he possible p edic i e ac o s, AR,
AERD, ecu en NP, he need o egula in anasal co -
icos e oid ea men , p eope a i e pe o al co icos e-
oid, p e ious sinus su ge y and/o polypec omy, and
e hmoidec omy pe o med as a pa o cu en su ge y
we e signi ican ly p edic i e o e ision su ge y
(P<0.03) (Table II). No o he co a ia e was signi ican ly
p edic i e su ge y ecu ence. An ochoanal polyps did
no a ec he esul (Table II). Each o he p e iously
men ioned se en signi ican p edic i e a iables was
en e ed in o he adjus ed Cox’s p opo ional haza d
model. In his mul i a iable analysis, AR, pe o al o
in anasal co icos e oid ea men , and ecu en NP
we e signi ican ly p edic i e o su ge y ecu ence
(Table II). Thus AR, co icos e oid, ea men and ecu -
en NP seems o p edic independen ly su ge y
ecu ence.
DISCUSSION
The clinically mos use ul p edic i e ac o s would
be speci ic, sensi i e, easy, and usable ac oss nonselec ed
CRS popula ions. Thus, his s udy was implemen ed o
e alua e simple ac o s associa ing he e ision a e o
he e ogeneous CRS popula ion wi h bo h CRSsNP and
CRSwNP pheno ypes and wi h inclusion o also less
se e e cases. The mos signi ican inding was ha he
ac o s associa ing signi ican ly wi h he ecu ence o
su ge y we e AR, ecu en NP, pe o al o in anasal
co icos e oid ea men , and p e ious su ge y. These
ac o s associa ed wi h he numbe o e ision ope a-
ions, and hey also independen ly p edic ed he need
o e ision su ge y in he su i al analyses.
To he knowledge o he au ho s, he e exis only
wo p e ious s udies on ecu en sinus su ge y using
su i al analysis echnique. Mendelsohn e al. pe -
o med a su i al analysis o a coho o 549 CRSwNP
pa ien s who unde wen ESS o e a 10-yea pe iod.
16
Re ision su ge y occu ed a a high a e, especially in
pa ien s wi h as hma, AERD, o on al sinus disease. In
ou s udy popula ion o bo h CRSsNP and CRSwNP
pa ien s, we we e able o demons a ed associa ion
be ween ecu en NP and p e ious ope a ion(s); how-
e e , we we e no able o demons a e independen asso-
cia ion o as hma o AERD wi h ecu en su ge y. This
migh e lec he di e ences in ou s udy popula ions.
Wu e al. e iewed eco ds o 299 CRSwNP pa ien s who
unde wen wo o mo e su ge ies om 1987 h ough
2011.
17
They ound ha e ision su ge y and eg ow h
o nasal polyps appea s o be a ec ed by smoking and
ope a i e echnique bu no by o he ac o s such as
as hma o ad anced CT s age. The pe o mance o mid-
dle u bina e esec ion in his s udy popula ion was
ound o signi ican ly delay he ime un il e ision su -
ge y; howe e , he bene icial e ec o u binec omy
appea ed o dissipa e by 8 yea s. In ou s udy, smoking
did no p edic su ge y ecu ence; he e o e, u he
s udies on his a e equi ed.
Wu e al. ound ha he mean numbe o su ge ies
pe o med pe CRSwNP pa ien was 2.3, and he mean
ime be ween sinus su ge ies was 4.9 yea s.
17
Con-
as ed o his, in ou s udy he median numbe o e i-
sion su ge ies du ing ollow-up was 0 in bo h CRSsNP
and CRSwNP g oups. Howe e , we ound ha he
highe numbe o e ision su ge ies associa ed wi h he
his o y o AR, AERD, ecu en NP, p e ious sinus su -
ge y and/o nasal polypec omy, and he egula need o
in anasal co icos e oid and p eope a i e co icos e oid,
which e lec s he p e ious indings.
17
Mo e s udies exis on e ision a e, especially in
CRSwNP pa ien s wi hou using su i al me hod. A
s udy showed ha male pa ien s and younge adul
pa ien s we e ound o ha e highe e ision a es
13
;
howe e , we we e no able o demons a e his. In addi-
ion, Chang e al. ound ha pa ien s wi h as hma o
alle gic hini is had highe e ision a es compa ed
wi h hose pa ien s wi hou hese como bidi ies.
13
This
is in pa in line wi h ou indings ha alle gic hini is
TABLE I.
(Con inued)
Re ision Sinus Su ge y and/o Polypec omy in
5 Yea s
No (N 5161) Yes (N 517)
N%N%PValue
E hmoidec omy pe o med as a pa o cu en su ge y
No 109 67.7 6 35.3 .010
Yes 52 32.3 11 64.7
P alues by Fishe
s exac es .
1
Uncinec omy-only in one side and uncinec omy 1an os omy on he o he side o each pa ien .
AERD 5aspi in-exace ba ed espi a o y disease; ACP 5an ochoanal polyp; ESS 5endoscopic sinus su ge y; maxill. 5maxilla y (sinus); NP 5nasal
polyps.
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independen ly p edic ed ecu en su ge y. The e iology
be ween alle gy and hinosinusi is is mul i ac o ial,
and a clea consensus o hei ela ion does no exis a
p esen . Howe e , p e ious s udies sugges a opy being
a p edisposing ac o o CRS. I has been pos ula ed
ha pa ien s wi h alle gic hini is ha e edema ous
nasal mucosa, impai ed cilia unc ion, and o e p oduc-
ion o sec e ions, which lead o blockage a he si e o
os iomea al complex, impai ed d ainage and en ila-
ion, and again o sinus p oblems.
28
Recen ly, Wilson
Fig. 1. Compa ison o numbe o e ision sinus ope a ions and/o e ision nasal polypec omies in di e en CRS pa ien g oups du ing
ollow-up o in a e age 9 yea s. CRS pa ien g oup (A) wi h/wi hou he p esence o alle gic hini is. (B) The p esence o aspi in-
exace ba ed espi a o y disease. (C) The egula use o in anasal co icos e oid. (D) P eope a i e pe o al co icos e oid cou se. (E) Recu -
en nasal polyps. (F) P e ious sinus su ge y and/o nasal polypec omy.
P alues by Fishe
s exac es .
AERD 5aspi in-exace ba ed espi a o y disease; CRS 5ch onic hinosinusi is.
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e al. e iewed 24 a icles examining he ela ionship o
alle gy and CRSsNP and/o CRSwNP.
29
Acco ding o hei
analysis, he ole o alle gy in CRSwNP and CRSsNP con-
inues o be con o e sial, wi h he le el o e idence
poo .
29
We ecen ly demons a ed ha sensi iza ion o
o e i e common ai bo ne alle gens and o se e al alle -
gen g oups associa e s ongly wi h adul as hma.
30
I
could be specula ed ha mul iple alle gen sensi iza ion
migh be associa ed wi h p og essing CRS, whe eas sim-
ple pollen alle gic hini is does no associa e wi h se e e
CRS. Al hough no ye p o en, his could in pa explain
con o e sial indings o he associa ion be ween
CRS(wNP) and a opy. Thus, u u e s udies on sensi iza-
ion pa e ns and he associa ion wi h CRS p og ession
would be impo an o unde s and he mechanisms behind
CRS de elopmen , p e en ion o CRS, and i s p og ession.
The p esence o gene al diseases did no associa e wi h
ecu en su ge y. To he knowledge o he au ho s, he e
Fig. 2. P edic i e e ec o di e en ac-
o s o he ime un il e ision sinus su -
ge y and/o nasal polypec omy was
pe o med acco ding o he Kaplan-
Meie me hod. (A) P edic i e e ec o a
pa ien his o y o doc o -diagnosed alle -
gic hini is in all CRS pa ien s (N 5174).
(B) P edic i e e ec o a pa ien his o y
o doc o -diagnosed AERD in all CRS
pa ien s (N5178). (C) P edic i e e ec
pa ien - epo ed egula need o in a-
nasal co icos e oid ea men in all CRS
pa ien s (N 5169). (D) P edic i e e ec
o p eope a i e pe o al co icos e oid
ea men in all CRS pa ien s (N 5172).
(E) P edic i e e ec o p e ious sinus
su ge y and/o nasal polypec yomy in all
CRS pa ien s (N 5177). (F) P edic i e
e ec o ecu en nasal polyps in all
CRS pa ien s (N5178). (G) P edic i e
e ec o maxilla y sinus ope a ion ech-
nique in all he CRS pa ien s who unde -
wen cu en maxilla y sinus su ge y
(N5146). (H) P edic i e e ec o maxil-
la y sinus ope a ion echnique in he
subg oup o CRSsNP pa ien s who
unde wen cu en maxilla y sinus su -
ge y (N 581).
P alues by log- ank es .
AERD 5aspi in-exace ba ed espi a o y
disease; CRS 5ch onic hinosinusi is;
CRSsNP 5ch onic hinosinusi is wi hou
nasal polyps; ESS 5endoscopic sinus
su ge y; mini-in asi e ESS 5uncinec-
omy-only in one side and uncinec o-
my 1an os omy on he o he side o
each pa ien .
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a e no epo s o he e ec o gene al diseases on he ecu -
ence o CRS su ge y. The e ec o occupa ional exposu e
has p e iously been s udied. Hox e al. pe o med a ques-
ionnai e s udy wi h 890 pa ien s who had unde gone one
o mo e ESS, and wi h 182 con ols.
18
A e adjus men s,
he au ho s de ec ed ha he p e alence o occupa ional
exposu es associa ed signi ican ly wi h he numbe o ESS
p ocedu es. The au ho s concluded ha exposu e a wo k
appea s o be a isk ac o o he occu ence o CRS and
o i s ecu ence o pe sis ence, as e idenced by he need
o e ision su ge y.
18
In his cu en s udy, we we e no
able o comp ehensi ely s udy he e ec o occupa ional
exposu e o e ision a e because he occupa ional da a
was a ailable om only abou 40% o he pa ien s.
Pe o ming e hmoidec omy as a pa o cu en su ge y
was associa ed wi h ecu en CRS su ge y. A e adjus -
men , e hmoidec omy did no associa e wi h e ision su ge y.
Thismigh bedue o he ac ha hemajo i yo hosewho
TABLE II.
Unadjus ed and Adjus ed Cox’s P opo ional Haza d Models o Va iables Analyzed Fi ed o Need o Re ision Sinus Su ge y and/o Nasal
Polypec omy Du ing Follow-up o A e age 9 Yea s.
Re ision Sinus Su ge y and/o Polypec omy
Uni a ia e Mul i a iable
E en s
(23) HR 95% CI PValue HR 95% CI PValue
Gende
Male 9 1 No en e ed
Female 14 1.54 0.67–3.56 .31
Age
<40 yea s 8 1 No en e ed
40 yea s 15 0.77 0.33–1.82 .56
Alle gic hini is
No 8 1 1
Yes 15 2.86 1.21–6.76 .017 3.97 1.34–11.73 .013
As hma
No 12 1 No en e ed
Yes 11 1.71 0.76–3.88 .20
AERD
No 16 1 1
Yes 7 3.37 1.38–8.23 .008 0.34 0.076–1.48 .15
P e ious and/o cu en nasal polyps
No o ACP
1
7 1 No en e ed
Yes 16 2.31 0.94–5.68 .07
Recu en nasal polyps
No 16 1 1
Yes 7 5.08 2.07–12.45 <.001 5.77 1.37–24.3 .017
Smoke s
No 21 1 No en e ed
Yes 2 0.34 0.08–1.45 .15
Need o egula in anasal co icos e oid
No 4 1 1
Yes 19 6.63 2.26–19.49 .001 4.64 1.47–14.68 .009
P eope a i e pe o al co icos e oid
No 16 1 1
Yes 6 5.13 2.00–13.15 .001 9.27 1.89–45.40 .006
P e ious sinus su ge y and/o nasal polypec omy
No 11 1 1
Yes 12 5.06 2.23–11.49 <.001 2.50 0.60–10.36 .21
E hmoidec omy pe o med as a pa o cu en su ge y
No 9 1 1
Yes 14 2.70 1.17–6.27 .021 0.48 0.13–1.80 .28
The six a iables ha en e ed he adjus ed Cox’s p opo ional haza d we e chosen om hose ha we e s a is ically signi ican a iables in unadjus ed
Cox’s p opo ional haza d models.
1
When emo ing ACP om he analysis, he esul emained simila .
ACP 5an ochoanal polyp; AERD 5aspi in-exace ba ed espi a o y disease; CI 5con iden ial in e al; HR 5haza d a io.
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unde wen p ima y e hmoidec omy we e NP pa ien s, and
he s a us o ecu en NP had s onge independen associa-
ion wi h he need o e ision su ge y han e hmoidec omy.
A s udy sugges s ha p ima y ESS ailu e is mos
o en associa ed wi h e-obs uc ion in he a ea o he os io-
mea al complex.
13
We demons a ed he e ha a minimally
in asi e ope a ion sligh ly and insigni ican ly inc eased
he e ision a e in he CRSsNP subg oup; howe e , mini-
mally in asi e app oaches (e.g., balloon sinuplas y and
uncinec omy-only) did no ha e an e ec on he e ision
a e when obse ing all CRS pa ien s. In e ms o he need
o ecu en CRS su ge y, a minimally in asi e echnique
migh be su icien ; howe e , ou p e ious con olled s udy
demons a es ha adiological eco e y was sligh ly in e-
io a e uncinec omy-only echnique compa ed o an os-
omy.
25
Mo eo e , i is highly impo an o u he ollow
up he ecu ence o su ge ies in pa ien s wi h balloon sin-
uplas y because he balloon sinuplas y p ocedu es we e
s a ed in Finland in 2008.
We ound ha p e ious su ge y was pe o med in
abou 26% o CRSwNP pa ien s and o a signi ican ly
lowe ex en in CRSsNP pa ien s (7.5%). In acco dance
wi h ou indings, a s udy obse ed a e ision a e in
CRS 4,484 pa ien s who had unde gone ESS.
13
The
s udy g oup ound ha he numbe o pa ien s who
unde wen e ision ESS was 528 (11.78%). Ano he
s udy g oup in es iga ed 1,249 CRS pa ien s and 221
con ols in Uni ed Kingdom by means o a sel -
adminis e ed ques ionnai e.
2
A o al o 396 (57%)
pa ien s wi h CRSwNPs/alle gic ungal hinosinusi is
(AFRS) epo ed ha ing unde gone p e ious endoscopic
nasal polypec omy; o hose, 182 o he 396 (46%)
epo ed ha ing ecei ed mo e han one ope a ion.
2
In
compa ison, su gical a es in pa ien s wi h CRSsNPs
we e signi ican ly lowe : 13% o cases speci ically
epo ed ESS; and o hose, only 30% epo ed mul iple
p ocedu es.
2
The easons o highe pe cen age o p e i-
ous su ge y in he s udy o Philpo e al. compa ed o
ou s migh be ela ed o di e ences in he popula ions,
s udy design, and managemen o CRS pa ien s.
2
We ound ha only abou one- en h o CRS pa ien s
equi ed e-ope a ion in 5 yea s. A s udy showed ha e i-
sion su ge y a es a 5 yea s we e 10%, 25%, and 37% o
con ol pa ien s, pa ien s wi h as hma, and pa ien s wi h
AERD, espec i ely.
16
P io s udies ha e epo ed ecu -
ence a es in sho e mean ollow-up pe iods (less han 5
yea s) o be ween 21% and 66% o CRSwNP, bu mos did
no subdi ide among pa ien g oupings o did no commen
on e ision su ge y a es.
16,31–37
Philpo e al. showed he highes a e o e ision
su ge y o be among hose wi h CRSwNPs and AFRS,
wi h a es o p e ious su ge y almos wice ha o hose
wi hou nasal polyps, which is suppo ed by he U.K.
Sinonasal Audi .
2
We also demons a ed he e a clea
associa ion o CRSwNP pheno ype wi h bo h inc eased
p io ope a ion(s), as well as ecu en NP as an inde-
penden p edic o o e ision du ing ollow-up. The e is
a g owing accep ance ha pa ien s wi h and wi hou
polyps ha e dis inc di e ences. This is e lec ed in he
cu en i e a ion o EPOS, wi h di e en ea men algo-
i hms o he wo main pheno ypes.
1,2
In line wi h his,
we showed ha ecu en NP was an independen p e-
dic i e ac o o ecu ence o su ge y.
S udies sugges ha a c ucial ac o in he success
o ailu e o su gical in e en ion will be pa ien compli-
ance wi h ongoing medical managemen pos ope a-
i ely.
2
The au ho s sugges ed ha his may cu en ly
be coun e ac ed by di e ing ad ice om p ima y and
seconda y ca e p ac i ione s and emphasizes he need
o g ea e awa eness o guidelines; howe e , he e is
also a need o u he clinical ials in e ms o medical
ea men o unde pin his.
2
We ound ha egula
in anasal co icos e oids did no delay ecu ence o
su ge y; in con as , hey associa ed wi h inc eased e i-
sion a e. Regula in anasal co icos e oid ea men ,
which mos pa ien s epo ed o con inue o use egu-
la ly also pos ope a i ely, p edic ed independen ly
inc eased e ision a e. Mo eo e , he need o p eope a-
i e pe o al co icos e oid cou se p edic ed independ-
en ly inc eased e ision a e. The need o egula
in anasal and p eope a i e pe o al co icos e oids
would pu a i ely e lec se e e CRSwNP and uncon-
olled CRS (wi h/wi hou a opy). Toge he , i seems ha
a mo e se e e/uncon olled CRS pheno ype could be
iden i ied. I migh be ela ed o ecu en NP and a opy
bu migh be independen o AERD and as hma. Despi e
maximum managemen , his pheno ype migh need e-
quen su gical in e en ions. The pu a i e easons o
p og ession o CRS in hese pa ien s migh be gene ic
and immunological, a ec ing in e ac ions be ween hos
ba ie immuni y and en i onmen al i i an s/mic obes.
7
These pa ien s do no ully espond he cu en ea -
men wi h co icos e oids and su ge y, and a e hus in
high need o ad anced managemen such as biological
ea men and o he u u e he apeu ic in e en ions.
This s udy did no measu e polyp eg ow h o o he
signs o uncon olled CRS, which would ha e e lec ed
mo e p ecisely he p og essing CRS. Re ision CRS su -
ge y was chosen as he end poin because he e is a lack
o good objec i e da a o CRS p og ession. Se ial nasal
endoscopy shows nasal polyp eg ow h bu has limi ed
co ela ion wi h he se e i y o CRS(sNP)
38
; and se ial
sinus CT scans canno be pe o med due o adia ion.
Thus, we obse ed he ecu en su ge y as a clea ly
de ined e en , which indi ec ly e lec s o CRS p og es-
sion. This s udy did no dis inguish be ween e ision
CRS su ge y due o subop imal su ge y and o ecu -
ence o CRS. This s udy also did no measu e di e en-
ces in pos ope a i e medical ea men s ha could a ec
iming o e ision su ge y. Ou scope was o de ec p e-
dic i e ac o s ha would associa e wi h ecu en CRS
su ge y independen o hese ac o s and despi e he e o-
genei y in CRS popula ion.
This s udy has se e al limi a ions. The sample was
he e ogeneous and small in size o clinically ele an
conclusions. No CRS cases wi h cys ic ib osis o wi h
p ima y cilia y dyskinesia we e a ailable o his s udy.
A sho coming is ha he diagnosis o AR was no based
on skin-p ick es posi i i y in all pa ien s; and he diag-
nosis o AERD was no based on nons e oidal an i-
in lamma o y d ugs challenge es in all pa ien s. The e
also migh ha e been limi a ions in he collec ion o
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