This article has been accepted for publication and undergone full peer review but has not been Type of article: Systematic review with meta-analysis
Title:
Benefits of Nasal Saline Treatment in Acute Rhinosinusitis:
Systematic Review and Meta-Analysis
Short title: saline treatment in acute sinusitis Authors:
Wirach Chitsuthipakorn, MD1,2 ORCID 0000-0002-9787-6767 Dichapong Kanjanawasee, MD3,4 ORCID 0000-0003-2681-2958 Minh P. Hoang, MD, MSc5,6,7 ORCID 0000-0001-8878-2905 Kachorn Seresirikachorn, MD, PhD6,7 ORCID 0000-0002-0158-7638 Kornkiat Snidvongs, MD, PhD6,7 ORCID 0000-0001-7537-4718
1 Center of Excellence in Otolaryngology, Head & Neck Surgery. Rajavithi Hospital, Bangkok, Thailand
2 College of Medicine, Rangsit University, Bangkok, Thailand
3 Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
4 Center of Research Excellence in Allergy & Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
5 Department of Otolaryngology, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam
6 Department of Otolaryngology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
7 Endoscopic Nasal and Sinus Surgery Excellence Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
Corresponding author and postal address Kornkiat Snidvongs, MD, PhD
Faculty of Medicine, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand Telephone +6622564103 Fax +6622527787
Email: [email protected]
Declarations: None
Ethics approval: None
Funding: None
Acknowledgment: None
Authorship contribution:
WC: Study concept and design, study search and screening, bias evaluations, data extraction, data analysis, first manuscript drafting. DK: Study search and screening, bias evaluations.
MPH: Bias evaluations, data extraction, data analysis. KSe: manuscript edits. KSn: Study concept and study design, data analysis, manuscript edits. All authors approved the final manuscript.
Conflict of interest:
None of the authors has any conflict of interest related to this study.
Financial disclosures:
Wirach Chitsuthipakorn, Dichapong Kanjanawasee, Minh P. Hoang, and Kachorn
Seresirikachorn have no disclosure. Kornkiat Snidvongs has served on the speaker‟s bureau for Merck Sharp Dolme, Viatris, AstraZeneca, and Menarini.
Keywords: acute rhinosinusitis, nasal saline treatment, quality of life, endoscopy, adult
Word count: 3053
ABSTRACT Background
Although nasal saline treatments are widely used in treating acute rhinosinusitis (ARS), the evidence in adult patients is inconclusive. Our objective was to assess the add-on benefits of saline treatment in adult with ARS.
Methods
Literature searches were performed (updated May 9th, 2021). Randomized controlled trials studying the effects of nasal saline treatment in adults with ARS were included. Data were pooled for meta-analysis. Outcomes were composite symptoms score (CSS), disease-specific quality of life (DS-QoL) score, individual symptom score, endoscopy score, saccharin transit time, cure rate, days to resolution, and adverse events.
Results
Eleven studies (718 patients) were included. Nasal discharge was the only symptom improved [standardized mean difference (SMD) -0.36, 95% confidence interval (CI) -0.66 to -0.05]. Saline as an add-on treatment brought no benefits in: CSS and DS-QoL score at both time points (3-10 days and at the end of the study). Other outcomes also showed no benefits of saline, including endoscopy score, saccharin transit time, cure rate, days to resolution, and adverse events. Subgroup analyses showed improvement in viral ARS patients in CSS (SMD -0.60, 95% CI -1.12 to -0.08) and DS-QoL score (mean difference -15.90, 95% CI -31.78 to - 0.02), and patients using large-volume saline in CSS (SMD -0.42, 95% CI -0.78 to -0.06).
Conclusions
Nasal saline as an add-on treatment improved rhinorrhea. There was no improvement in CSS and DS-QoL except the subgroup of viral ARS when using large-volume saline. There were no differences in adverse events between the saline and non-saline treatments.
Word count: 249
INTRODUCTION
Nasal saline treatment is recommended as an option in chronic disorders of the nose and paranasal sinuses.1 The „no recommendation‟ in acute rhinosinusitis (ARS) given by The European Position Paper on Rhinosinusitis and Nasal Polyps 2020,2 and the „option‟
recommendation given by the International Consensus Statement on Allergy and Rhinology:
Rhinosinusitis 2021,3 are based on meta-analysis and randomized control trials (RCTs) which showed unclear results.
Nasal saline treatment mechanically washes out mucous secretion and debris from the nose and the middle meatus. It improves the mucociliary function, which should decrease nasal symptoms and enhance the effects of intranasal corticosteroids.4 Evidence of saline treatment in ARS is inconclusive due to multiple factors that may impact its effectiveness. Previous meta-analyses assessed patients with upper respiratory tract infection, including pharyngitis, otitis media, and tonsillitis.5,6 However, the aim of nasal saline treatment is for nasal mucociliary clearance. Therefore, it is unlikely that the patients with infection of other parts would benefit from the nasal saline treatment. Furthermore, recommendations for adult with ARS are based on meta-analyses which assessed infants, children6 or mixed populations.5 Differences in anatomy of the nose, the paranasal sinuses, hypertrophic adenoids and the horizontal angle of the eustachian tube could impact the effects of nasal saline treatment.
There is no meta-analysis that exclusively assesses the benefits of nasal saline added to the standard treatment in adults. Other factors, such as devices, delivery methods, and regimens of nasal saline treatment may also influence the penetration and the rinsing effects of nasal saline treatment.
The objective of this study was to evaluate the effects of nasal saline treatment as an adjunctive treatment in adult patients with ARS compared to standard treatment alone
without saline (non-saline group). In addition, it aimed to assess the impact of device used for delivering the saline and saline tonicity.
METHODS
This systematic review was registered in PROSPERO (CRD42021249573). The study selection was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA-2020).7
Eligibility Criteria
RCTs studying the add-on effects of nasal saline treatment in adult patients with ARS were included. ARS was defined following the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2020 and categorized into 2 subgroups: (1) common cold or acute viral rhinosinusitis (AVRS) and (2) acute bacterial rhinosinusitis (ABRS).2 The diagnostic criteria of AVRS used in this study were (1) symptoms or signs of ARS with a duration of less than 10 days and (2) no worsening symptoms or signs of ARS. Patients who did not meet the criteria for AVRS were categorized as ABRS.8 Studies assessing mixed population of ARS and other diseases were included if the data of ARS patients were extractable. Studies with add-on nasal saline treatment by any volume, pressure, frequency, and duration were included.
Studies with medicated saline, active ingredients, or additive substances other than mineral/salt were excluded. Studies that gave standard treatments unequally to each study group were excluded. Standard treatments included intranasal corticosteroids and antibiotics (for ABRS patients). We excluded studies assessing other medicine where saline treatment was used as a control. There was no language restriction. The comparisons were (1) standard treatment plus nasal saline treatment versus standard treatment only, (2) isotonic versus hypertonic nasal saline treatment, and (3) between different types of devices.
Information Sources and Search Strategy
Electronic searches were conducted with the last update on May 9th, 2021. Databases were MEDLINE, EMBASE, Web of Science, Scopus, and Cochrane library. Manual searches were also done in Google Scholar, ResearchGate, and medrxiv.org. Relevant published systematic reviews were cross-checked for the references. The search strategy is provided in Supplement 5 (Appendix).
Study Selection Process
Two reviewers (WC, DK) independently performed title and abstract screening based on the predetermined criteria and reviewed full-text of the selected articles. Disagreement was resolved by verbal discussion or consultation with the corresponding author. The study selection process was done using a web-based systematic tool (www.covidence.org).
Data Extraction
Two reviewers (WC, MPH) independently extracted data from the included RCTs. If there was insufficient information or conflicting data, the corresponding author of that article was contacted for further information.
Data from studies with mixed populations of ARS and other diagnoses were extracted separately when possible. Low-volume device was defined when a device delivered <60 ml of saline and large-volume device when a device delivered ≥60 ml of saline. The data were pooled for meta-analysis following the Cochrane handbook 6.2 instructions.9
Primary outcomes were composite symptom score (CSS), individual symptom score, disease- specific quality of life (DS-QoL) score, days to resolution, cure rate, saccharin transit time (STT), endoscopy score, and adverse events. Secondary outcomes were the impact of saline tonicity (isotonic vs hypertonic) and devices (low-volume vs large-volume) on the effects of nasal saline treatment. Symptoms and DS-QoL were collected at 2 time points: (1) 3-10 days
(2) the end of the study. When multiple outcomes were reported within one period, the earliest outcome was extracted. Other outcome data were collected at the end of the study.
Data Synthesis
Risk ratio (RR) and 95% confidence interval (CI) were used for dichotomous data. When there was a zero value in any cell, risk difference (RD) was used. Standardized mean difference (SMD) or Mean difference (MD) and 95% CI were used for continuous data. A p value <0.05 was considered significant. The heterogeneity in the estimates of treatment effects from different trials was assessed by the I2 statistic. A fixed-effect method was used when the statistical heterogeneity was low (I2<25%). When the statistical heterogeneity was high, a random-effect method was used for a more conservative estimate of the differences.
To explore the heterogeneity, subgroup analyses by presumed pathogens (AVRS and ABRS) and devices (spray, syringe, cup, pot, atomizer, squeeze bottle) were investigated. Statistical assessments were performed using Review Manager 5.4.1.
Risk of Bias of individual Study
Two independent reviewers (WC, DK) assessed risk of bias of each study using the Revised Cochrane risk-of-bias tool (RoB2).10 Disagreement was resolved by verbal discussion or by the corresponding author.Six domains were assessed: randomization process, deviation from intended interventions, missing outcome data, measurement of the outcome, selection of the reported result, and overall bias. “Low risk of bias” was defined when the methods used for each domain were clearly described. “High risk of bias” was defined when plausible bias that seriously weakened confidence in each domain was shown under the description. “Some concerns” was defined when there was not enough information to determine.
RESULTS
Study Selection
During title and abstract screening, 886 records were removed. Twenty-six full texts were assessed. Ten RCTs5,11–19 were selected from electronic databases, and one RCT in Thai20 was from the manual search. The study selection flowchart is displayed in Figure 1.
Participants
There were 718 participants with a mean age of 36.6 years (eight RCTs11–14,16,18–20). The age ranged from 27 to 44 years old and 34.6% were male (eight RCTs11–14,16,17,19,20). Three RCTs included patients with ABRS,14,18,20 six RCTs included AVRS,5,13–17 and the other 2 RCTs included a mixed population of ABRS and AVRS.11,19
Intervention
Six RCTs assessed the effects of saline versus non-saline treatments,5,11,13,18–20 four RCTs assessed the effects of hypertonic versus isotonic saline,15,16,18,19 and three RCTs assessed the impact of devices on nasal saline treatment.12,14,17
The type of device included simple spray (three RCTs),5,16,19 10-20 ml syringe (five RCTs),12,14,15,17,20 atomized douche (one RCT),17 250 ml irrigation bag (one RCT),14 250 ml squeeze bottle (one RCT),11 100 ml cup saline (one RCT),13 and not mentioned in one RCT.18 Duration of treatment ranged from 10 minutes12,16 to four weeks.20 The remaining eight RCTs assessed the effects between 1-3 weeks. Characteristics of all the included studies with their main results are shown in Table 1.
Risk of bias in the included studies
Overall, nine out of 11 included studies had high risks of bias. The “measurement of the outcome” was the most frequent high risk of bias (six RCTs) due to unblinded assessors (Supplement Figure 1A). Six RCTs (55%) had low risk of bias in the randomization process.
Five RCTs (45%) had low risk of bias in the deviation from intended interventions. Eight
RCTs (73%) had low risk of bias in the missing outcome data. Three RCTs (27%) had low risk of bias in the measurement of the outcomes. Nine RCTs (82%) had low risk of bias in selection of the reported results (Supplement Figure 1B).
Comparison I (Saline versus non-saline treatment) 1.1 Composite symptom scores (CSS)
Four RCTs compared the CSS between the saline and non-saline groups.11,13,19,20 There were no significant differences between groups at 3-10 days (SMD -0.16, 95% CI -0.28 to 0.60, p=0.47, 3 RCTs, I2=60%),11,19,20 and at the end of the study (SMD -0.11, 95% CI -0.71 to 0.48, p=0.71, 3 RCTs, I2=74%).11,13,20
Subgroup analysis by presumed pathogens showed the favourable effect of saline treatment only in the AVRS subgroup (SMD -0.60, 95% CI -1.12 to -0.08, p=0.02, 2 RCTs, I2=27%).11,13 There were no benefits of saline in the ABRS subgroup (SMD 0.37, 95% CI - 0.07 to 0.82, p=0.10, 2 RCTs, I2=0%),11,20 and mixed population (SMD 0.31, 95% CI -0.07 to 0.69, p=0.11, 1 RCT).19
Subgroup analysis by saline volume showed the favorable effects of saline treatment in the large-volume subgroup, 250 ml bottle and 100 ml cup (SMD -0.42, 95% CI -0.78 to -0.06, p=0.02, 2 RCTs, I2=0%).11,13 However, the effects favoured non-saline treatment in the low- volume subgroup, 20 ml syringe and spray (SMD 0.38, 95% CI 0.06 to 0.69, p=0.02, 2 RCTs, I2=0%).19,20 The analyses are displayed in Figure 2A-D.
1.2 Disease-specific quality of life (DS-QoL)
Two RCTs compared the 20/22-items Sino-nasal outcome test questionnaires (SNOT-20/22) between the saline and non-saline groups.11,20 There were no differences in SNOT scores between groups at 3-10 days (MD -0.53, 95% CI -6.94 to 5.89, p=0.87, 2 RCTs, I2=0%)11,20 and at the end of the study (MD 0.05, 95% CI -5.32 to 5.42, p=0.16, 2 RCTs, I2=50%).11,20
One study used a generalized QoL score (0-100) and found no difference between groups.
The data of this study were not pooled into the meta-analysis.13 Subgroup analysis by presumed pathogens showed the favorable effect of saline treatment in the AVRS subgroup (MD -15.90, 95% CI -31.78 to -0.02, p=0.05, 1 RCT)11 but not ABRS (MD 3.02, 95% CI - 2.54 to 8.57, p=0.29, 2 RCTs, I2=0%).11,20 Subgroup analysis by saline volume showed that neither the low-volume (20 ml syringe) nor large-volume subgroup (250 ml bottle) had benefits over the non-saline treatment (Figure 3A-D).
1.3 Individual symptom score
Three RCTs reported individual symptom scores.11,13,20 Of the four symptoms, nasal discharge was the only symptom that significantly improved by nasal saline irrigation compared to non-saline treatment at the end of the study (SMD -0.36, 95% CI -0.66 to -0.05, p=0.02, 3 RCTs, I2=0%).11,13,20 The results are displayed in Supplement Figure 2.
1.4 Endoscopy score
There was one RCT that reported no difference in the modified Lund-Kennedy score improvement between the saline and non-saline treatment at the end of the study (MD 0.12, 95% CI -0.80 to 1.04, p=0.80).11
1.5 Saccharin transit time (STT)
One RCT showed that the improvement of STT was not different between the saline irrigation and non-saline treatment at the end of the study (MD -0.07, 95% CI -4.29 to 4.15, p=0.97).18
1.6 Cure rates and Days to resolution
The cure rates between the nasal saline treatment, using 250 ml irrigation, and non-saline groups were comparable in one study.11 At the end of the first week, the patients were cured at 36.7% vs 51.6% (RR 0.71, 95% CI 0.40 to 1.27, p=0.31), and 90.0% vs 93.5% at the end of the study (RR 0.96, 95% CI 0.83 to 1.12, p=0.67) in the nasal saline and non-saline
groups, respectively.11 Three RCTs reported that the duration of days to resolution was not different between the nasal saline treatment and non-saline group (MD -1.17, 95% CI -3.20 to 0.87, p=0.26, 3 RCTs, I2=69%).5,13,19 The results are displayed in Supplement Figure 3.
1.7 Adverse events
There were three studies that assessed adverse events.11,19,20 Adam et al. reported that saline caused nasal irritation 15 times and dry nose 18 times.19 There were no adverse events reported in the other two studies.11,20 When the data were pooled, nasal saline treatments did not significantly cause adverse events compared to non-saline. The risk difference (RD) between groups for nasal irritation was 0.07 (95% CI -0.09 to 0.24, p=0.39, 3 RCTs), and for dry nose was 0.09 (95% CI -0.11 to 0.29, p=0.38, 3 RCTs).11,19,20 The results are displayed in Table 2A.
Comparison II (Hypertonic saline versus isotonic saline) 2.1 Symptom score
Data from one RCT showed a comparable effect on symptom scores between two tonicities (MD -1.10, 95%CI -2.25 to 0.05, p=0.06).19
2.2 Saccharin transit time
Three RCTs showed that STT was not different between two tonicities (MD -0.98, 95% CI - 2.32 to 0.36, p=0.15, 3 RCTs, I2=0%).15,16,18 The results are displayed in Supplement Figure 4.
2.3 Adverse events
Two RCTs reported the adverse events.16,19 Nasal irritation and burning were found more frequently in hypertonic than isotonic saline in one study (MD 1.40, 95% CI 0.96 to 1.84, p<0.01),16 but not in the other (RR 2.58, 95% CI 0.92 to 7.27, p=0.07).19 The data from these two studies were different in variables and could not be pooled. Dry nose was not different
between the two tonicities (RR 0.60, 95% CI 0.27 to 1.35, p=0.21).19 The results are displayed in Table 2B.
Comparison III (Comparison of different devices) 3.1 Symptom score
Gelardi et al. found that nasal obstruction was improved more in the large-volume saline (250 ml irrigation bag) compared to the low-volume (10 ml syringe, MD 2.00, 95% CI 0.82 to 3.18, p<0.01).14 Passali et al. reported significant symptom score improvement in the atomized nasal douche group (p<0.01) but not in the 20 ml syringe group.17 Their SDs were not reported and could not be imputed.17 Piromchai et al. reported that nasal saline irrigation using a syringe with a silicone tip had higher patient preference than a syringe without the tip.12 The outcomes reported in their study were not the outcomes of interest of our review.
3.2 Saccharin transit time
SD was not given and could not be imputed.17
DISCUSSION
Saline treatment did not improve CSS and DS-QoL. Subgroup analysis by presumed pathogen showed that the patients with AVRS had significant improvements in CSS and DS- QoL. Subgroup analysis by saline volume showed that the patients who used large-volume saline had a significant improvement in CSS. Based on our findings, saline treatment should be recommended to a selected group of patients with ARS.
Nasal saline treatment significantly improved the symptom of rhinorrhea. As nasal symptoms of the patients with AVRS are mainly rhinorrhea and nasal obstruction, these patients should benefit from saline irrigation which mechanically washes out the nasal discharge. This is
contrast to patients with ABRS who have greater symptom severity than AVRS, including facial pain, fever, and double sickening.
There were comparable the treatment effects between isotonic and hypertonic saline.
However, there were more nasal irritation and burning, reported in the hypertonic saline group.16 Overall, these adverse events were minor and tolerable.21 Because the possible side effects in hypertonic saline may outweigh the overall benefit, isotonic saline should be more encouraged for patients with ARS.
Different devices impact the penetration of saline into the posterior part of the nose, and its treatment effects. A study found that a 250 ml squeeze bottle decreased nasal obstruction more than a 10 ml syringe.14 These results support the greater benefit of large-volume saline shown in the subgroup analysis. However, when two low-volume devices were compared, the 7-8 ml atomized saline douche improved CSS, but the 20 ml syringe did not.17 This could be due to the atomized douche distributing the compressed micronized mist onto a greater area than a conventional syringe despite its lower saline volume. One excluded survey study assessing 418 patients with chronic and acute rhinosinusitis reported ear pain in the patients using the large-volume device.22 These adverse events were not found in the patients in our review who were instructed to use a topical decongestant before performing large-volume nasal saline irrigation if they had nasal congestion.11
To the best of our knowledge, this review is the first meta-analysis that assesses the effects of saline treatment exclusively in adult patients with ARS. A prior systematic review included children and adults patients with pharyngitis, tonsillitis, otitis media and were analyzed without population stratification.5 It showed that nasal saline treatment did not offer benefits to patients with ARS. Our main results were in line with their analyses; however, we provided additional analyses that help physicians select appropriate device and saline regimens for selected patient subgroups. Another previous meta-analysis was done in
pediatric patients with ARS.6 In line with our study, it concluded that nasal saline relieved rhinologic symptoms while our analyses revealed that saline improved the symptom of rhinorrhea in ARS adult patients and improved the CSS and DS-QoL in the AVRS subgroup.
Based on the data from the included studies in our analysis,11,13,20 we suggest that patients with AVRS should rinse their noses with isotonic saline using a large volume device for at least twice a day. The saline volume should be around 100-250 ml.11,13 Furthermore, the patients may wash until they get back to premorbid status or two weeks at most, where nearly all patients are cured.11
This review had several limitations. The number of included studies for each meta-analysis is limited. Of the total 11 studies, data were pooled from four studies for the CSS and two studies for the DS-QoL. Nine of the 11 studies have an overall high risk of bias. Data from King et al. (2012) were unpublished; the details were taken from the meta-analysis of the Cochrane group.5 Although subgroup analyses were investigated, heterogeneity still existed in some subgroups. Evidence of nasal saline treatment for patients with ABRS was still unclear. Future well-conducted RCTs focusing on adult ABRS which assessed the effects of large-volume nasal isotonic saline irrigation, are required.
CONCLUSIONS
Nasal discharge was the only symptom that significantly improved by nasal saline. Add-on benefits on CSS and DS-QoL were not identified for adult patients with undifferentiated ARS, but benefits were shown separately in subgroups of patients with AVRS and patients using a large-volume device. Saline was safe, but nasal irritation was found more frequently in hypertonic than isotonic saline.
ACKNOWLEDGEMENT: None
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TABLES AND FIGURES
Table 1. Characteristics of the included studies. Footnote: URI: upper respiratory tract infection, AR: allergic rhinitis, ARS: acute rhinosinusitis, AVRS: acute viral rhinosinusitis, ABRS: acute bacterial rhinosinusitis, CRS: chronic
rhinosinusitis, RMM: rhinomanometry, ARM: acoustic rhinometry, STT:
saccharin transit time, VAS: visual analog scale, WURSS:Wisconsin upper respiratory symptom survey, EQ-VAS: EuroQol visual analog scale, GSS:
global symptom score, OTC: over the counter, SNOT: sino-nasal outcome test questionnaire, Roman number I-V: patient group 1-5
Table 2. Adverse events of saline treatments. A: Saline versus non-saline control, B:
Hypertonic saline versus isotonic saline. Footnote: 95%CI: 95% confidence interval, n/a: stated by the author but no number was given, SD: standard deviation
Figure 1. Diagram of study selections based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement 2020
Figure 2. Comparison of saline versus non-saline groups: The composite symptom score. A At 3-10 days, B: At the end of studies, C: Subgroup analysis by acute rhinosinusitis subtypes, D: Subgroup analysis by saline volume. Footnote:
95%CI: 95% confidence interval, SD: standard deviation, IV: inverse variance
Figure 3. Comparison of saline versus non-saline groups: The disease specific quality- of-life score. A: At 3-10 days, B: At the end of the study, C: Subgroup analysis by acute rhinosinusitis subtypes, D: Subgroup analysis by saline volume. Footnote: 95%CI: 95% confidence interval, SD: standard deviation, IV: inverse variance
Supplement Figure 1. Risk of bias summary. A: Risk of bias domains for each included study, B: Risk of bias item presented as percentages across all included studies
Supplement Figure 2. Comparison of saline versus non-saline groups: Individual symptom scores
Supplement Figure 3. Comparison of saline versus non-saline groups: Cure rates and days to resolution
Supplement Figure 4. Comparison of hypertonic saline versus isotonic saline:
Saccharin transit time
Supplement 5 (Appendix). Search strategy in each database
Footnote: URI: upper respiratory tract infection, AR: allergic rhinitis, ARS: acute
rhinosinusitis, AVRS: acute viral rhinosinusitis, ABRS: acute bacterial rhinosinusitis, CRS:
chronic rhinosinusitis, RMM: rhinomanometry, ARM: acoustic rhinometry, STT: saccharin transit time, VAS: visual analog scale, WURSS:Wisconsin upper respiratory symptom survey, EQ-VAS: EuroQol visual analog scale, GSS: global symptom score, OTC: over the counter, SNOT: sino-nasal outcome test questionnaire, Roman number I-V: patient group 1-5
