10.14639/0392-100X-N2279
Objectives. The Sino-Nasal Outcome Test 22 (SNOT‑22) is a validated patient-reported outcome instrument to evaluate the health-related quality of life (HRQoL) in patients with chronic rhinosinusitis (CRS). There are no published normative SNOT‑22 scores, limiting its interpretation. Methods. Symptom scores from 1,000 SNOT‑22 questionnaires were analysed by principal component analysis (PCA) and exploratory factor analyses. Data were derived from a survey with 1,000 healthy Europeans (reference cohort) who were recruited using the Respondi panel for market and social science research. This subsample was quoted to the population distribution of the German Microcensus and selected from a non-probability panel.Results. The overall normative SNOT‑22 score can be detected to be 20.2 ± 19.44. Male (18.49 ± 19.15) and older (&gt; 50 years old; 18.3 ± 17.49) participants had overall lower SNOT‑22 mean results than females (21.8 ± 19.6) and younger (21.4 ± 20.55) participants, indicating higher levels of satisfaction. PCA proposed two SNOT‑22 domains (“physiological well-being” and “psychological well-being”), which explained 65% of the variance. Conclusions. These are the first published (German) normative scores for the SNOT‑22 and provide a clinical reference point for the interpretation of data.
text/xml
1827-675X
2279
en
Karim Zaoui
http://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
patient-reported outcome measures
Normative data for interpreting the SNOT‑22
Text.Serial.Journal
https://www.actaitalica.it/
43
Rhinology
2023-10-10
2022-08-15
2023-12-19
2023-12-19
390-399
1
Karim Zaoui
2023/10/10
10.14639/0392-100X-N2279
390
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Heidelberg, Heidelberg, Germany
1827-675X
patient-reported outcome measures
en
399
Normative data for interpreting the SNOT‑22
https://www.actaitalica.it/article/download/2279/1042
43
ACTA OTORHINOLARYNGOLOGICA ITALICA 2023;43:390-399; doi: 10.14639/0392-100X-N2279




Rhinology


Normative data for interpreting the SNOT‑22
Valori di riferimento per interpretare lo SNOT‑22
Michaela Plath1, Matthias Sand2, Carlo Cavaliere3, Peter K. Plinkert1, Ingo Baumann1, Karim Zaoui1
1
 Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Heidelberg, Heidelberg, Germany; 2 GESIS-Leibniz-
Institute for the Social Sciences, Mannheim, Germany; 3 Department of Sense Organs, Sapienza University of Rome, Rome, Italy


SUMMARY
Objectives. The Sino-Nasal Outcome Test 22 (SNOT‑22) is a validated patient-reported
outcome instrument to evaluate the health-related quality of life (HRQoL) in patients with
chronic rhinosinusitis (CRS). There are no published normative SNOT‑22 scores, limiting
its interpretation.
Methods. Symptom scores from 1,000 SNOT‑22 questionnaires were analysed by princi-
pal component analysis (PCA) and exploratory factor analyses. Data were derived from a
survey with 1,000 healthy Europeans (reference cohort) who were recruited using the Re-
spondi panel for market and social science research. This subsample was quoted to the pop-
ulation distribution of the German Microcensus and selected from a non-probability panel.
Results. The overall normative SNOT‑22 score can be detected to be 20.2 ± 19.44. Male
(18.49 ± 19.15) and older (> 50 years old; 18.3 ± 17.49) participants had overall lower
SNOT‑22 mean results than females (21.8 ± 19.6) and younger (21.4 ± 20.55) participants,
indicating higher levels of satisfaction. PCA proposed two SNOT‑22 domains (“physiologi-
cal well-being” and “psychological well-being”), which explained 65% of the variance.
Conclusions. These are the first published (German) normative scores for the SNOT‑22 and
provide a clinical reference point for the interpretation of data.
KEY WORDS: Sino-Nasal Outcome Test 22, normative score, functional endoscopic sinus
surgery, chronic rhinosinusitis, patient-reported outcome measures
                                                                                                   Received: August 15, 2022
                                                                                                   Accepted: March 5, 2023
RIASSUNTO                                                                                          Published online: October 10, 2023
Obiettivi. Il Sino-Nasal Outcome Test 22 (SNOT‑22) è uno strumento validato per valutare
la qualità della vita nei pazienti affetti da rinosinusite cronica (CRS). Tuttavia, non esistono   Correspondence
in letteratura punteggi di riferimento per lo SNOT‑22, limitandone l’interpretazione.              Michaela Plath
Metodi. I punteggi dello SNOT‑22 di 1.000 individui sani sono stati analizzati mediante l’a-       Department of Otorhinolaryngology, Head and
nalisi delle componenti principali (PCA) e l’analisi fattoriale esplorativa. I dati sono stati     Neck Surgery, University Hospital Heidelberg,
ricavati da un’indagine su cittadini dell’Europa centrale, reclutati utilizzando il pannello       Ruprecht-Karls-University, Im Neuenheimer Feld
Respondi per le ricerche di mercato e di scienze sociali.                                          400, D-69120 Heidelberg, Germany
Risultati. Il punteggio di riferimento complessivo dello SNOT‑22 è stato in media pari             Tel. +49 (0)6221 5635684
a 20,2 ± 19,44. I partecipanti maschi (18,49 ± 19,15) e oltre i 50 anni (18,3 ± 17,49)             E-mail: michaela.plath@med.uni-heidelberg.de
avevano risultati complessivamente inferiori rispetto ai partecipanti di sesso femminile
(21,8 ± 19,6) e giovani (21,4 ± 20,55), indicando livelli più elevati di soddisfazione. La           How to cite this article: Plath M, Sand
PCA ha proposto due domini SNOT‑22 (“benessere fisiologico” e “benessere psicologi-                  M, Cavaliere C, et al. Normative data for
co”), che spiegavano il 65% della varianza.                                                          interpreting the SNOT‑22. Acta Otorhi-
Conclusioni. Questi sono i primi punteggi normativi pubblicati (in Germania) per lo                  nolaryngol Ital 2023;43:390-399. https://doi.
SNOT‑22 e possono fornire un riferimento clinico per l’interpretazione del questionario.             org/10.14639/0392-100X-N2279

PAROLE CHIAVE: Sino-Nasal Outcome Test-22, valori di riferimento, chirurgia funzionale             © Società Italiana di Otorinolaringoiatria
endoscopica dei seni paranasali, rinosinusite cronica, patient-reported outcome measures           e Chirurgia Cervico-Facciale


                                                                                                                  OPEN ACCESS
Introduction                                                                                       This is an open access article distributed in accordance with
                                                                                                   the CC-BY-NC-ND (Creative Commons Attribution-Non-
Chronic rhinosinusitis (CRS) is a common and debilitating condition with                           Commercial-NoDerivatives 4.0 International) license. The
significant economic impact 1, which poses a considerable burden to health-                        article can be used by giving appropriate credit and mention-
                                                                                                   ing the license, but only for non-commercial purposes and
care providers and patients. Patients with worse sinus-specific quality-of-life                    only in the original version. For further information: https://
(QoL) impairment are more likely to pursue functional endoscopic sinus sur-                        creativecommons.org/licenses/by-nc-nd/4.0/deed.en




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                                                                                        Normative data for interpreting the SNOT-22




gery (FESS), whereas those with less symptomatic burden        Materials and methods
are more likely to continue medical therapy alone 2.
                                                               Recruitment and patient data
There is a growing acceptance that the patient’s opinion
                                                               1,000 German individuals (reference cohort) were recruited
is essential in providing high-quality health care. The Eu-
                                                               via a non-probabilistic online panel. The subset of the panel
ropean position paper on rhinosinusitis and nasal polyps
                                                               used for this study was quoted to relevant population distri-
(EPOS) 2020 recommends subjective assessment of chron-
                                                               butions of the German Microcensus (an annual 1% probabil-
ic rhinosinusitis symptoms in research and in clinical prac-
                                                               ity sample of the German population) 15. Relevant parameters
tice using validated questionnaires 3.
                                                               were age, gender, region and education. Migration was also
The Sino-Nasal Outcome Test 22 (SNOT‑22) is a well-val-
                                                               considered but not quoted for. The reference cohort was re-
idated 4, disease-specific instrument that combines rhino-
                                                               cruited from September 2018 using the Respondi panel, an
logic issues (physical problems and functional limitations)
                                                               international organisation for standardisation (ISO)-certified
with general health issues (e.g., emotional domains) 5. Be-
                                                               online access panel for market and social science research.
cause of its reliability, validity, responsiveness and easy
                                                               The participation was voluntary but compensated with an ex-
application 6, the SNOT‑22 is considered to be the most
                                                               pense allowance. Due to the nature of a cohort derived from
suitable patient-reported outcome measure (PROM) for
                                                               the general public, the sample size was decided on to en-
evaluating patients with CRS. The 4-subdomain struc-           sure a small sampling error and smaller confidence intervals,
ture for SNOT‑22 (reflecting sleep, nasal, otologic/facial     since the presence of participants with low (or high) QoL-
pain, and emotional symptoms of CRS) was validated as          measures was expected to be less pronounced. Sociodemo-
the most appropriate for a total of 800 patients with CRS      graphic questions were asked first. Second, the SNOT‑22
from eastern and western United States by using confirma-      questionnaire was completed by the study participants. Raw
tory factor analysis (CFA) 7.                                  data were cleaned and converted into a labeled Statistical
There are still no normative scores for the SNOT‑22 ques-      Package for Social Sciences (SPSS) dataset before check-
tionnaires. It is not yet known how the QoL of CRS pa-         ing that questions were complete and relevant quotas were
tients undergoing FESS compares with that of a mean-           distributed. Test groups were screened to make sure the right
ingful control population. Normative scores have been          questions had been asked. Statistical analysis was conducted
published for disease-specific questionnaires before and       by GESIS (Leibniz Institute for Social Sciences).
after septorhinoplasty, which allow rhinosurgeons to pre-
dict and evaluate the outcome of rhinosurgery 8. Previous      Disease-specific QOL questionnaire
studies have proposed different tools to evaluate the effect   We used the German validated version of the Sino-Na-
of CRS on the patient’s quality of life. Obviously, baseline   sal Outcome Test-22 (SNOT‑22) 16,17 to measure health-
SNOT‑22 seems to be one of the most important factors          related quality of life (HRQoL) in patients with CRS 4.
affecting outcomes 9 and several studies have suggested its    SNOT‑22 is the modified version of SNOT-20, which has
prognostic role in terms of achievement of improvement         been validated by Piccirillo et al. 18, and to which two car-
and risk of revision surgery 10. Thus, measurements of the     dinal CRS symptoms, “stuffed nose” and “difficulty to
proportion of CRS patients receiving a minimal clinically      feel smells or tastes”, have been added 19. The resulting
important difference (MCID) 11-14 and the percentage of        SNOT‑22 was validated in English by Hopkins and col-
relative improvement (RI) 13,14 after FESS based on their      leagues 4. SNOT‑22 covers a broad range of health-related
pre-operative QoL level have been performed. However,          QoL problems, including physical problems, functional
pre-operative CRS patients are not “normal” because            limitations and emotional consequences 19. The ques-
they carry the physical and psychological burdens caused       tionnaire is converted into a score of 0-110, with higher
by CRS. Thus, normative SNOT‑22 scores may provide             scores indicating a greater impact on QoL. All questions
a clinical reference point for the interpretation of data.     are based on a 0-5 scale, where 0 defines no problems
Therefore, the main aim of our study was to provide the        with the given symptom and 5 defines the maximum prob-
first normative values for the SNOT‑22 as an additional        lems. According to Feng et al., the outcomes it measures
decision-making tool after FESS by performing a sys-           can be divided into four different clinical subscales: sleep,
tematic prospective study on 1,000 healthy participants.       nasal, otologic/facial pain, and emotional symptoms
Moreover, the secondary objective of the study was to          (Cronbach’s alpha > 0.7) 7. The translation and cultural
simplify the previously common four-component model            adaptation of the SNOT‑22 questionnaire was carried out
for the SNOT‑22 by using principal component and ex-           in accordance with the guidelines and standards for the
ploratory factor analysis.                                     translation and cultural adaptation of PROMs as recom-



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M. Plath et al.




mended by the ISPOR Task Force 20. For the questionnaire          ed parameters and a fixed sample size. Participants were
all rights are reserved; Copyright 2006, The Washington           sampled from an existing (opt-in) access panel until a par-
University in St. Louis, Missouri.                                ticular quota was filled.

Statistical analysis                                              Influence of sociodemographic aspects on the overall,
The data were analysed using the statistical software R (ver-     psychological and physiological assessment
sion 3.5.2). Utilising the libraries psych, nFactor and Facto-    Regarding the influence of the sociodemographic aspects
MineR, Principal Component Analyses (PCA) and Explora-            on the overall, psychological and physiological assessment
tory Factor Analyses (EFA) were conducted. To determine           measured by SNOT‑22, age and female gender signifi-
the number of main components, graphical and non-graphi-          cantly affected the overall and psychological component
cal PCAs were used, including Scree Plots and the analyses        (p < 0.01), whereas the physiological component was only
of the models Eigenvalues, Parallel Analysis and the deter-       influenced by age. Tests for correlation showed only a low,
mination of optimal coordinates using the methods suggest-        but significant linear relationship in case of age (overall:
ed by Kaiser 21 and Cattell 22. For the latter EFA, we used the   r = - 0.09; p = 0.006; physical: r = - 0.09; p = 0.006; psy-
“standard” regression estimation suggested by Thomson 23,         chological: r = - 0.07; p = 0.02), however, the regression
while the Varimax procedure was chosen for rotation (al-          analysis (Tab. I) showed a significant effect on the mag-
though we cannot be certain that the main components are          nitude of the SNOT‑22 values. Old age is defined as older
actually independent). Generally, this assumption can be ex-      than 50 years and young age as less than 50 years. There
pected to be met, when variables only (significantly) load on     was a negative linear relationship between the age and the
one particular factor (above |0.3|) while having “zero-load-      SNOT‑22 score: as the age increased, the SNOT‑22 score
ings” on any other factor. Furthermore, factors are expected      decreased, indicating higher levels of satisfaction (Fig. 1A).
not to be described by all existing variables, if there is more   Young and old participants differed significantly in results
than one factor. If the assumptions are not met, the influ-       of SNOT‑22 overall score (21.4 [± 20.6] vs 18.3 [± 17.5]),
ence of particular variables on any factor may be over- or        psychological (27 [± 27.2] vs 23.5 [± 23.4] and physiolog-
underestimated, which may lead to false conclusions. The          ical (17.6 [± 19.1] vs 14.6 [± 15.8]) (p < 0.01). Moreo-
underlying results show that the assumption is met for most       ver, male participants had lower SNOT‑22 questionnaire
variables, while there are some that load on more than one        results than female participants (Fig. 1B). Comparing
particular factor. However, in those cases, the difference in     men (n = 500) and women (n = 500) by t-test, they dif-
loadings is distinctive enough to assume that the decision for    fered highly significantly from each other regarding the
a particular variable to load on a factor may still be valid.     SNOT‑22 overall (18.5 [± 19.2] vs 21.8 [± 19.6]) and psy-
After the initial PCAs and EFAs, the two main components          chological components (22.6 [± 25.3] vs 28.7 [± 27.3])
indicating a physical and a psychological constituent were        (p < 0.01), but not concerning the SNOT‑22 physiological
identified. Since our interest was also to explore which de-      aspect (15.7 [± 17.7] vs 17.1 [± 18.1]) (p = 0.20). No influ-
mographics contribute to which part of these components,          ence of marital status, residence state, educational level, or
a subdivision of the SNOT‑22 into two sub-indices was             employment status was ascertainable.
performed and regression analyses as well as students t-
tests and tests for correlations of key-characteristics were      PCA of the SNOT‑22 and EFA of the identified
conducted. For that purpose, we rescaled the sub-indices          two-domain SNOT‑22 structure
to a range from 0-110 to have a better comparability to-          In this study, the 22 items were methodologically reduced
wards the total outcomes of SNOT‑22. Aside from the coef-         into subsets of symptoms by using PCA. The PCA pro-
ficients, residual standard errors, results of the students’ t-   posed at least two SNOT‑22 domains (“physiological well-
statics and p-values are reported below. A p-value less than      being” and “psychological well-being”), which explained
0.05 was considered statistically significant.                    65% of the total variance. All factor loadings were > 0.5.
                                                                  Graphical (Scree and Biplot; Fig. 2), as well as non-graph-
                                                                  ical attempts (Fig. 3), were used (Parallel Analysis and
Results                                                           Optimal Coordinates) to distinguish the number of major
Clinical characteristics                                          components contributing to the overall SNOT‑22-Score.
1,000 participants (500 males and 500 females) were sam-          The graphical analysis suggested three major components,
pled. The mean age of the participants was 44.3 ± 14.2            whereas non-graphical suggested only two. Therefore, the
years. The response rate is not reported since participants       EFA was calculated separately for two and three compo-
belong to a non-probabilistic open access panel with quot-        nents. However, the inclusion of a third component did lit-



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Table I. Regression-Table of overall SNOT-22 values, physical and psychological well-being by sociodemographic characteristics.
                                                                 SNOT‑22                   Physical well-being              Psychological well-being
 Constant                                                       29.483***                     17.633**                            46.601***
                                                                 (7.933)                        (7.333)                            (10.732)
 Age                                                            -0.170***                      -0.131**                           -0.227***
                                                                 (0.057)                        (0.053)                             (0.077)
 Gender: female                                                 3.555***                         1.935                            5.894***
                                                                 (1.307)                        (1.209)                             (1.769)
 Marital status: married                                           0.651                         1.485                              -0.554
                                                                 (1.513)                        (1.398)                             (2.046)
 Marital status: divorced                                          2.216                         1.067                               3.876
                                                                 (2.156)                        (1.993)                             (2.917)
 Marital status: widowed                                          -2.995                        -1.822                              -4.690
                                                                 (4.162)                        (3.847)                             (5.630)
 State: Bavaria                                                  -4.916*                        -3.966                              -6.287
                                                                 (2.861)                        (2.645)                             (3.871)
 State: Berlin                                                   -2.038                         -2.451                              -1.441
                                                                 (4.390)                        (4.058)                             (5.939)
State: Brandenburg                                               -2.114                         -0.750                              -4.083
                                                                 (4.545)                        (4.201)                             (6.148)
State: Bremen                                                    -2.915                         -3.646                              -1.859
                                                                 (5.160)                        (4.770)                             (6.981)
State: Hamburg                                                   -5.244                         -5.243                              -5.244
                                                                 (3.463)                        (3.201)                             (4.684)
State: Hess                                                     -6.583**                      -7.607***                             -5.104
                                                                 (3.077)                        (2.845)                             (4.163)
State: Mecklenburg Western Pomerania                             -5.483                         -5.566                              -5.363
                                                                 (5.164)                        (4.774)                             (6.986)
State: Lower Saxony                                              -2.395                         -1.642                              -3.482
                                                                 (3.067)                        (2.835)                             (4.149)
State: Northrhine-Westphalia                                     -2.139                         -2.868                              -1.086
                                                                 (2.798)                        (2.587)                             (3.786)
State: Rhineland Palatinate                                      -2.008                         -1.310                              -3.016
                                                                 (3.154)                        (2.916)                             (4.267)
State: Saarland                                                  -1.826                          0.660                              -5.418
                                                                 (4.119)                        (3.808)                             (5.572)
State: Saxony                                                    -3.165                         -2.900                              -3.548
                                                                 (3.569)                        (3.299)                             (4.828)
State: Saxony-Anhalt                                             -6.640                         -5.700                              -7.997
                                                                 (4.363)                        (4.033)                             (5.903)
State: Schleswig-Holstein                                        -0.954                         -2.623                               1.457
                                                                 (3.321)                        (3.069)                             (4.492)
State: Thuringia                                                 -2.772                         -3.014                              -2.422
                                                                 (3.860)                        (3.568)                             (5.222)
Migration (if true) within EU                                    -0.120                         -1.853                               2.384
                                                                 (4.528)                        (4.185)                             (6.125)
Migration (if true) outside EU                                   -2.082                          1.277                              -6.934
                                                                 (4.205)                        (3.887)                             (5.689)
                                                                                                                                           continues   u




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M. Plath et al.




Table I. Regression-Table of overall SNOT-22 values, physical and psychological well-being by sociodemographic characteristics (follows).
                                                                 SNOT‑22                  Physical well-being               Psychological well-being
 Education: low                                                   -3.545                          4.501                               -15.168*
                                                                  (6.316)                        (5.839)                               (8.544)
 Education: mid                                                   -4.426                          3.785                               -16.286*
                                                                  (6.340)                        (5.860)                               (8.576)
 Education: high                                                  -5.259                          4.238                              -18.976**
                                                                  (6.364)                        (5.883)                               (8.609)
 Employment: not/no longer employed                                5.573                          2.727                                9.684*
                                                                  (4.246)                        (3.925)                               (5.744)
 Employment: sometimes                                             2.895                          0.415                                 6.478
                                                                  (4.643)                        (4.292)                               (6.281)
 Employment: part-time                                             0.138                         -1.533                                 2.552
                                                                  (4.358)                        (4.029)                               (5.896)
 Employment: full-time                                             3.690                          2.698                                 5.123
                                                                  (4.182)                        (3.866)                               (5.658)
 Observations                                                      1,000                          1,000                                 1,000
 Log likelihood                                                 -4,367.375                     -4,288.756                           -4,669.524
 Akaike's information criterion                                 8,794.751                      8,637.513                            9,399.048
Significance: * p < 0.05; ** p < 0.01; *** p < 0.001.




Figure 1. Forest plot showing the association of the SNOT‑22 with age (A) and gender (B). The questionnaire score is plotted on the y-axis, the frequency of
score responses on the x-axis. Lower scores of SNOT‑22 signify a more positive rating indicating higher levels of satisfaction.



394
                                                                                                                   Normative data for interpreting the SNOT-22




Figure 2. Biplot figure of our two-factor Principal Component Analysis. It is      Figure 3. Non-graphical analysis as elbow figure. The black curve, illustrat-
clearly visible that the participant cohort is divided in two groups concerning    ing the Eigenvalues in descending order, would suggest the inclusion of 3 main
the SNOT‑22 questionnaire. Comp. 1 and Comp. 2 are the first two Compo-            components, since any further Eigenvalues are below one. However, the par-
nents that will later be used as the sub-indices physiological and psychological   allel analysis (green), comparing the actual matrix of Eigenvalues to a Monte-
well-being. The “cloud” of numbers reflects the observations and their respec-     Carlo-simulated matrix of the same size, shows that only the EVs of two main-
tive case number, whereas the different variable names are represented in red.     components are above the 95th percentile. The same number of components
The arrow that stems from the graphs centroid and joins the variable name can      is suggested in regard of the EVs’ gradients and the optimal coordinates (red),
be used to determine the relatedness between the variables. The closer they        whereas the Acceleration Factor (blue) shows that the major shift in the slope
are, the higher the (positive) correlation between these variables. Arrows that    of this curve can be seen after the first component.
oppose each other in a 90°-angle can be considered as uncorrelated. Arrows
that go into a different direction are negatively correlated.


tle to improve the overall analysis. Indeed, using the third                       healthy participants. A first cross‑sectional study on nor-
component by individual and variable PCA factor map, a                             mative values with an adequate sample size of 539 healthy
clear assignment of test score categories could not be pro-                        volunteers, selected according to gender and age, was per-
duced, while the joint distributions of the factor loadings                        formed in Brazil by Gregorio et al. who concluded that the
seemed rather heterogeneous for all main components that                           range of 0‑8 points seemed to be more suitable as a “normal”
included the third one. In contrast to this, an individual and                     value for the SNOT‑22 instrument 24. Whether this is also
variable two-components-factor analysis showed a cluster-                          true for Europeans needed to be ascertained.
ing of variables on two main components. This makes PCA                            In our study, a SNOT‑22 score of 20.2 ± 19.4 has been
of utmost importance as ‘hypothesis generating’ tool creat-                        detected in 1,000 healthy Europeans, who were quoted to
ing a simple and clear two-factor construct including items                        relevant population distributions of the German Microcen-
of physical well-being (factor 1) and items of psychologi-                         sus. That our normative values are higher than previously
cal well-being (factor 2), as shown in Table II.                                   reported 4,24-28 could be due to the fact that the questionnaire
                                                                                   had general health domains such as “fatigue” or “difficulty
                                                                                   to sleep”, which may be associated with other non-reported
Discussion
                                                                                   or not-investigated medical conditions. Moreover, the dif-
To assess the HRQoL in CRS, the SNOT‑22 has become                                 ferent SNOT‑22 standard scores can be associated with the
the reference questionnaire 4. At present, the literature still                    difference in life and culture between the diverse nations.
lacks normative values of SNOT‑22 in a European general                            Additionally, we considered this reference cohort to be a
population with an adequate sample size. Previous major                            “healthy” cohort. Thus, the medical history of comorbidi-
fields of studies using SNOT‑22 was rather on comparing                            ties (allergy, asthma and aspirin sensitivity) or previous op-
pre- and postoperative HRQoL outcome of patients undergo-                          erations/trauma was not queried as our priority in recruiting
ing FESS 4,5. Hopkins et al., who were the first to validate the                   participants for the study was to obtain an adequate popula-
SNOT‑22 in the United Kingdom, employed the question-                              tion group that corresponded to the German Microcensus in
naire in 2,077 surgical patients and obtained a preoperative                       terms of characteristics such as age, gender, level of edu-
score of 41.7 4 and an overall SNOT‑22 score of 9.3 in 116                         cation and region. However, the presence of comorbidities



                                                                                                                                                            395
M. Plath et al.




Table II. SNOT‑22 divided by two main components: depending on the higher value, the variable was assigned to the respective factor 1 (physical well-being
item) or factor 2 (psychological well-being item) after explorative factor analysis.
  SNOT‑22                                                                                    Factor 1                          Factor 2
                                                                                   (physical well-being items)   (psychological well-being items)
 Need to blow nose                                                                     0.63
 Nasal blockage                                                                        0.58                                       0.34
 Sneezing                                                                              0.64
 Runny nose                                                                            0.69
 Cough                                                                                 0.64
 Postnasal discharge                                                                   0.75
 Thick nasal discharge                                                                 0.78
 Ear fullness                                                                          0.70                                       0.32
 Dizziness                                                                             0.56                                       0.44
 Ear pain                                                                              0.71
 Facial pain or pressure                                                               0.73
 Decreased sense of smell/taste                                                        0.62
 Embarrassed                                                                           0.67
 Difficulty falling asleep                                                             0.35                                       0.69
 Waking up at night                                                                                                               0.72
 Lack of good night’s sleep                                                                                                       0.82
 Wake up tired                                                                                                                    0.85
 Fatigue                                                                                                                          0.88
 Reduced productivity                                                                  0.31                                       0.82
 Reduced concentration                                                                 0.34                                       0.78
 Frustrated, restless, irritable                                                       0.35                                       0.76
 Sad                                                                                   0.32                                       0.70



known to affect SNOT‑22 results could play a role as po-                       likely to experience facility in adapting psychologically
tential confounders. Here, we used a well-established study                    to major changes in functional disabilities than younger
design with a large sample size of 1,000 participants that                     patients do. From a sociologic standpoint, women have
were recruited by an international organisation for stand-                     historically been considered more likely to report symp-
ardisation (ISO)-certified online access panel for market                      toms, seek medical care, and give poorer self-evaluation
and social science research. We assumed that the decision                      of health, which may bias data toward a greater effect of
to participate in the Respondi panel was not correlated to                     CRS on QoL in women 30. Further QoL studies reported
anything that may affect SNOT‑22 scores. Our reference                         that women have significantly lower QoL for the same
cohort thus corresponds to a patient cohort most closely                       objective level of disease 31, whereas other studies found
approximating a probabilistic patient cohort compared with                     no difference when controlling for depression or analys-
control cohorts used in other studies. The way the healthy                     ing only disease-specific variables 32. Gender differences
subjects were selected in further studies, only by the re-                     in CRS are poorly understood 33, strongly paced and merit
sponse of the subjects, may have included possible bearers                     further study.
of CRS who did not have their formal diagnosis and carries                     Because groupings of highly correlated symptoms were
the risk of bias.                                                              apparent from the SNOT‑22 questionnaires, nowadays nu-
Regarding the sociodemographic aspects, we could show                          merous PCA and EFA, proposing four SNOT‑22 domains,
that age and female gender significantly affected the over-                    “nasal symptoms”, “otologic symptoms”, “sleep symp-
all and psychological component, whereas the physiologi-                       toms”, and “emotional symptoms”, have already been car-
cal component was only influenced by age. Old and male                         ried out 7,19,34. Nevertheless, ambiguous factor loadings and
participants had lower SNOT‑22 results than young female                       problematic item-domain assignments remained. “Facial
volunteers, indicating a higher level of satisfaction. This is                 pain or pressure” was allocated to the “otologic symptoms”-
in line with previous studies 24,29. Older people may be more                  domain, however, this may better fit into the “nasal symp-



396
                                                                                          Normative data for interpreting the SNOT-22




toms”. “Reduced productivity”, “reduced concentration”           disorders, or asthma were not included in our SNOT‑22 anal-
and “frustrated/restless/irritable” as cardinal symptoms of      ysis, which is a further weakness of our study. Our primary
depression 35 assigned to “sleep symptoms”, although these       aim was to include presumed healthy study participants in
domains assigned better to “emotional symptoms” 34. Feng         our study who, because they were not affected by symptoms
et al. validated the subdomain structure of the SNOT‑22          and did not know our study objective (type of blinding), had
in an American patient collective by CFA and underlined          no incentive to bias the SNOT‑22 results or to complete the
that the use of PCA and EFA has resulted in inconsistent         SNOT‑22 responses in a directional manner. This should
clustering patterns of CRS symptoms throughout the lit-          avoid a confounding factor of selection bias or response shift
erature 7. Since we intended to initially explore how data       bias phenomenon, that often occur in patient-reported out-
for the SNOT‑22 are related and which dimensions could           come measures 37,38. Our study has several strengths. This
be determined, we preferred PCA together with EFA over           is the first study measuring the impact of CRS symptoms
CFA. However, a CFA may have been useful if we had had           in healthy volunteers by using SNOT‑22. In addition to the
a particular model on how the data are structured. Moreo-        Lund-Mackay score > 1 and SNOT‑22 value > 20 after a cy-
ver, the majority of such factor analyses have mainly been       cle of medical therapy appropriating indications to FESS ac-
performed in non-European CRS patients 7,19, while Euro-         cording to the EPOS guideline 3, normative SNOT‑22 scores
pean data are lacking 34. Here, we are pursuing different        can also be used as an additional decision-making tool.
goals than our predecessors by exploring the SNOT‑22’s           Comparing SNOT‑22 of CRS patients with normative values
underlying factorial structure in a healthy middle-Europe-       explains any differences in scores better than simply com-
an reference cohort. Since the third factor only provided        paring scores before and after surgery. Indeed, preoperative
about 5% more of explained overall variance, we suggested        CRS patients are not “normal” because they carry the physi-
a two-principal factor concept divided into “physiological       cal and psychological burdens of CRS. Normative scores
well-being” and “psychological well-being”. A plausible          advance the understanding of expected patient outcomes,
explanation for disparately reported SNOT‑22 subdomain           improve the patient-physician shared decision-making pro-
structures could be the presence of confounding variables        cess, and may help to reduce the risk of unwarranted practice
such as environment, socioeconomic status, cultural differ-      variation in the future.
ences, or climate (United States vs Europe) 7. Moreover,
it might also be possible for the healthy reference cohort
                                                                 Conclusions
to differ in that case from a patient cohort as well. The
22 items of the SNOT‑22 can be logically assigned to the         According to the EPOS guidelines 3, outcomes in patients
respective two subdomains, except for “difficulty falling        undergoing FESS should be evaluated with PRO instru-
asleep” loading on the “psychological” factor and feeling        ments, such as the SNOT‑22. PRO instruments generate
“embarrassed”, which fitted into the “physical” component.       useful data regarding satisfaction and FESS-related QoL.
However, we can share these assignments. Patients with           This study presents the first known normative values for the
impaired psychological well-being might have difficulty          SNOT‑22, which will be useful for head and neck surgeons
falling asleep because they feel stressed, sluggish, anxious,    and researchers in providing a clinical context to interpret
and sad. Feeling “embarrassed” causes not only psycholog-        SNOT‑22 data.
ical, but also physiological stress reactions. Indeed, CRS
has a substantial negative health impact, adversely affect-      Conflict of interest statement
ing mood, physical functioning and social functioning 36.        The authors declare no conflict of interest.
A weakness of our study is that the sample was a non-prob-
abilistic quota sample, so the data is more suited to descrip-   Funding
tive analysis; inference cannot be calculated. Therefore,        This research did not receive any specific grant from fund-
we have to assume that SNOT‑22 scores are independently          ing agencies in the public, commercial, or not-for-profit
distributed between those that opt-in and those that do not.     sectors.
Another limitation of our study is the homogeneity of the
European reference cohort presented here, which may not          Author contributions
be comparable to a more diverse or ethnic patient popula-        MP: designed and coordinated the study, participated in da-
tion. Minimising this demographic influence, a proportion        ta acquisition and analysis, interpreted the data and drafted
of persons with a migration background was included in our       the manuscript; MS: participated in data interpretation and
participant recruitment. In addition, influential factors such   statistical analysis; CC: interpreted data and revised the
as allergy, previous operations, nose/facial trauma, affective   manuscript; PKP: revised the manuscript; IB: participated



                                                                                                                                397
M. Plath et al.




in data interpretation and revision of the manuscript; KZ:                           Polyposis and Chronic Rhinosinusitis. Rhinology 2015;53:10-17.
                                                                                     https://doi.org/10.4193/Rhino13.217
designed and coordinated the study, participated in data ac-
                                                                                10
                                                                                     Rudmik L, Soler ZM, Hopkins C. Using post-operative SNOT‑22
quisition and analysis, critically revised the manuscript for                        to help predict the probability of revision sinus surgery. Rhinology
important intellectual content.                                                      2016;54:111-116. https://doi.org/10.4193/Rhino15.284
The authors made substantial contributions to the study.                        11
                                                                                     Steele TO, Rudmik L, Mace JC, et al. Patient-centered decision mak-
                                                                                     ing: the role of the baseline SNOT‑22 in predicting outcomes for med-
Ethical consideration                                                                ical management of chronic rhinosinusitis. Int Forum Allergy Rhinol
                                                                                     2016;6:590-596. https://doi.org/10.1002/alr.21721
This study was approved by the Ethics Committee of the                          12
                                                                                     Hopkins C, Rudmik L, Lund VJ. The predictive value of the pre-
Medical Faculty at the University of Heidelberg (project                             operative Sinonasal Outcome Test-22 score in patients undergoing
no. S-143/2020).                                                                     endoscopic sinus surgery for chronic rhinosinusitis. Laryngoscope
The research was conducted ethically, with all study pro-                            2015;125:1779-1784. https://doi.org/10.1002/lary.25318
cedures being performed in accordance with the require-
                                                                                13
                                                                                     Rudmik L, Soler ZM, Mace JC, et al. Using pre-operative SNOT‑22
                                                                                     score to inform patient decision for endoscopic sinus surgery. Laryn-
ments of the World Medical Association’s Declaration of                              goscope 2015;125:1517-1522. https://doi.org/10.1002/lary.25108
Helsinki.                                                                       14
                                                                                     Gallo S, Russo F, Mozzanica F, et al. Prognostic value of
All patients were informed about the study aims and pro-                             the Sinonasal Outcome Test 22 (SNOT‑22) in chronic rhi-
tocol, and participants were enrolled after giving informed                          nosinusitis. Acta Otorhinolaryngol Ital 2020;40:113-121.
                                                                                     https://doi.org/10.14639/0392-100X-N0364
written consent.                                                                15
                                                                                     Gabler S, Hoffmeyer-Zlotnik JHP, Krebs D. Gewichtung in
                                                                                     der umfragepraxis. Wiesbaden: Springer Fachmedien; 1994.
Data availability                                                                    https://doi.org/10.1007/978-3-663-08044-2
The datasets generated during and/or analysed during the                        16
                                                                                     Albrecht T, Beule AG, Hildenbrand T, et al. Cross-cultural adaptation
current study are available from the corresponding author                            and validation of the 22-item sinonasal outcome test (SNOT‑22) in
                                                                                     German-speaking patients: a prospective, multicenter cohort study. Eur
on reasonable request.                                                               Arch Otorhinolaryngol 2022;279:2433-2439. https://doi.org/10.1007/
                                                                                     s00405-021-07019-6
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