Effect of Postoperative Xylitol Nasal Irrigation on Patients with Sinonasal Diseases

Abstract

Objective

To examine the effect of xylitol nasal irrigation in a large sample size of patients who had undergone nasal surgery.

Study Design

Double-blinded randomized controlled crossover study.

Setting

Tertiary referral center.

Methods

The study included 100 patients with sinonasal disease who underwent endoscopic sinus surgery (ESS), septoplasty, or both concurrently. To identify patients with allergic sensitization, serum-specific immunoglobulin E levels were measured. Nasal symptoms were evaluated with the NOSE (Nasal Obstruction Symptoms Evaluation) and SNOT-20 (Sino-Nasal Outcome Test–20) and via visual analog scale (VAS) scores.

Results

In the ESS group (n = 34), the general nasal symptom score evaluated by the SNOT-20 showed significantly greater improvement in the xylitol group versus the saline group (P = .022). VAS symptom scores for sneezing (P = .003), headache (P = .02), and facial pain (P = .037) were also more improved in the xylitol group. In the septoplasty group (n = 39), the VAS score for nasal stuffiness showed a significantly greater improvement in the xylitol group when compared with the saline irrigation group (P = .001). Among the patients with allergic sensitization (n = 31), rhinorrhea symptoms improved significantly more in the xylitol group than in the saline group (P = .024). The preference survey showed that more than half of the patients in each surgical group preferred xylitol irrigation.

Conclusion

We found that xylitol nasal irrigation was useful in postoperative ESS and septoplasty care. For patients with allergic sensitization, rhinorrhea showed greater improvement in the xylitol group than in the saline group.

Keywords

xylitol nasal irrigation endoscopic sinus surgery septoplasty

Nasal irrigation is commonly performed after sinonasal surgery. After endoscopic sinus surgery (ESS), nasal irrigation improves mucociliary clearance, decreases mucosal edema, dilutes inflammatory mediators, and mechanically cleanses concentrated mucous.¹ Nasal irrigation was also shown to minimize or prevent crusting, clear infective debris, ensure moistening of the mucosa, and recover mucociliary function after septoplasty.²

Xylitol is effective for postoperative nasal irrigation due to its antibacterial characteristics, promotion of innate bactericidal mechanisms,^3-5 and antiadhesive effect.⁶ These effects could confer benefits for patients undergoing ESS or septoplasty. Mucosal injury can occur during surgery, and nasal symptoms may develop; there is also a risk of infection and inflammation. A pilot study was conducted in which patients with previous ESS underwent xylitol nasal irrigation.⁷ However, the sample size was relatively small (n = 15), and the symptom score was slightly worse after irrigation, which conflicts with the findings of other reports.^1,2,8-11 In this study, we used a larger sample size and examined the effect of xylitol nasal irrigation on patients who had undergone ESS or septoplasty (or both). We also compared the extent of nasal symptom relief between the saline and xylitol irrigation groups. The endoscopic outcomes were compared with a modified Lund-Kennedy scoring system.¹²

Materials and Methods

Study Design and Patients

This study was a double-blinded randomized controlled crossover study comparing 2 methods of nasal saline irrigation. The Institutional Review Board of Seoul St Mary’s Hospital (KC16OISI0910) approved this study, which was conducted in accordance with the Declaration of Helsinki. All patients gave informed consent before they were enrolled. The study included patients with sinonasal disease who underwent ESS, septoplasty, or both concurrently at Seoul St Mary’s Hospital from November 2016 to April 2018. Patients who had previously undergone sinonasal surgery or who had immunocompromised status, cystic fibrosis, primary ciliary dyskinesia, a history of head and neck irradiation, rheumatologic diseases, or active pregnancy were excluded.

All patients underwent septoplasty with same surgical technique. Quilting suture (through-and-through suture) was conducted for approximating bilateral septal mucosa, and Merocel (Medtronic, Minneapolis, Minnesota) packing was inserted and removed 1 day postoperatively. In ESS, there were no Draf 2B/3 cases among the enrolled patients. Also, the same packing material (NasoPore; Stryker, Kalamazoo, Michigan), the same debridement schedule (postoperative days 3, 17, 24, and 38), and the same procedure by a single surgeon (S.W.K.) were conducted for both study groups. All patients in this study received topical nasal steroids postoperatively and were educated about the use of topical nasal steroids during the entire period of study.

The study included 100 patients, and the study flowchart is presented in Figure 1 . Thirteen patients withdrew from the study: 6 in group A and 5 in group B were lost to follow-up, and 1 patient in each group showed upper respiratory infection symptoms during the study. To identify patients with allergic sensitization, serum-specific immunoglobulin E levels were measured. In this analysis, a specific immunoglobulin E level >0.35 for any common airborne allergen was defined as allergic sensitization. The crossover study design is illustrated in Figure 2 . A 7-day washout period was scheduled before changing irrigation material to minimize any residual bias.

Figure 1.

Patient flowchart.

Figure 2.

Study design. POD, postoperative day.

Materials

Xylitol

This study used unlabeled sealed packages containing 4 mg of pharmaceutical-grade xylitol (Xlear, Inc, American Fork, Utah) and 2 mg of sodium. The patients received 50 of these packages and were instructed to mix the contents of 1 package with 240 mL of distilled water in a nasal irrigation bottle, followed by bilateral nasal irrigation 3 times a day. They were instructed to use 1 envelope per day for 14 days.

Normal Saline

Standard buffered isotonic salt (NeilMed, Santa Rosa, California) was repackaged into sealed unlabeled packages. Fifty packages were given to the patients, who were instructed to mix the contents with 240 mL of distilled water in an irrigation bottle. These patients were also instructed to use 1 package per once 3 times a day for 14 days.

The sealed xylitol and salt packages were divided into 2 number-encoded envelopes. The patients were instructed to perform a nasal irrigation 3 times a day for 14 days, from postoperative day 3 onward, using the contents of the first sealed envelope. After the 7-day washout period, patients performed nasal irrigation in the same manner for 14 days with the other sealed envelope. A random-number generator was used to randomize the order of irrigation in a double-blinded fashion. Symptom questionnaires were distributed to the patients and collected by an independent coordinator throughout the study.

Outcome Measures

Nasal symptoms were evaluated with the Nasal Obstruction Symptoms Evaluation (NOSE)¹³ and Sino-Nasal Outcome Test–20 (SNOT-20)¹⁴ and via visual analog scale (VAS) scores. The VAS assessment covered nasal obstruction, sneezing, rhinorrhea, snoring, headache, facial pain, and olfactory changes.¹⁵ The symptom questionnaires were distributed and collected at the outpatient clinic on postoperative days 3, 17, 24, and 38.

Statistical Analysis

All data are provided as mean ± SD. Student’s t test was used to compare the demographic characteristics between the groups. NOSE, SNOT-20, and VAS score changes (pre- vs posttreatment) were analyzed with a mixed effects model,⁷ as were the effects of treatment. A P value <.05 was regarded as statistically significant. SAS software (version 9.4; SAS Institute, Cary, North Carolina) was used to analyze the data.

Results

The mean age of the patients in group A (n = 43) was 41.9 ± 15.6 years: 33 (76.7%) of these patients were male and 10 (23.3%) were female. The mean age in group B (n = 44) was 43.4 ± 17.3 years: 33 (75.0%) of these patients were male and 11 (25.0%) were female. There was no statistical difference between the groups in terms of demographic characteristics (age, P = .686; sex, P = .851).

In the ESS group (n = 34), the general nasal symptom score evaluated by SNOT-20 showed significantly greater improvement in the xylitol group as compared with the saline group (P = .022; Table 1 ). VAS symptom scores for sneezing (P = .003), headache (P = .02), and facial pain (P = .037) were also more improved in the xylitol group. However, the degree of change in modified Lund-Kennedy score showed no difference between the groups (P = .466). Subanalysis was carried out to evaluate the effect of preoperative existence of nasal polyp in the ESS group. Patients with chronic rhinosinusitis without nasal polyp (CRSsNP) showed results similar to those of the entire ESS group (SNOT-20, P = .012; VAS for sneezing, P = .006; VAS for headache, P = .019; VAS for facial pain, P = .005; Table 2 ). However, patients with chronic rhinosinusitis with nasal polyp (CRSwNP) showed no significant difference between groups, unlike patients with CRSsNP ( Table 3 ). In the septoplasty group (n = 39), the degree of change in general nasal symptoms (NOSE and SNOT-20 scores) showed no significant difference between groups. However, the VAS score for nasal stuffiness showed a significantly greater improvement in the xylitol group versus the saline irrigation group (P = .001; Table 4 ). Within the combined-surgery group, there was no statistically significant difference in any change score between the xylitol and saline groups ( Table 5 ). Among the patients with allergic sensitization (n = 31), rhinorrhea symptoms improved significantly more in the xylitol group than in the saline group (P = .024; Table 6 ).

Table 1.

Symptom Changes between the Xylitol and Saline Irrigation Treatments among Patients Who Underwent Endoscopic Sinus Surgery (n = 34).

	Score Change, Mean ± SD		P Value
	Xylitol	Saline	P Value
NOSE	5.2 ± 7.9	2.3 ± 7.3	.119
SNOT-20	12.8 ± 17.2	4.3 ± 11.9	.022^a
VAS
Nasal stuffiness	1.7 ± 3.7	1.1 ± 2.6	.432
Sneezing	1.0 ± 1.9	−0.4 ± 2.1	.003^a
Rhinorrhea	1.7 ± 2.8	0.5 ± 2.2	.053
Snoring	0.6 ± 3.0	0.5 ± 2.3	.822
Headache	1.5 ± 2.4	0.3 ± 1.7	.020^a
Facial pain	1.1 ± 2.4	−0.1 ± 2.3	.037^a
Olfactory change	1.6 ± 2.2	1.3 ± 2.9	.611
Modified Lund-Kennedy score	2.9 ± 1.9	2.5 ± 1.7	.466

Abbreviations: NOSE, Nasal Obstruction Symptoms Evaluation; SNOT-20, Sino-Nasal Outcome Test–20; VAS, visual analog scale.

P < .05.

Table 2.

Symptom Changes between the Xylitol and Saline Irrigation Treatments among Patients with Chronic Rhinosinusitis without Nasal Polyp Who Underwent Endoscopic Sinus Surgery (n = 26).

	Score Change, Mean ± SD		P Value
	Xylitol	Saline	P Value
NOSE	5.6 ± 7.7	1.9 ± 7.9	.174
SNOT-20	13.0 ± 17.9	3.9 ± 12.0	.012^a
VAS
Nasal stuffiness	1.6 ± 3.6	0.7 ± 2.2	.359
Sneezing	1.0 ± 1.7	−0.3 ± 2.0	.006^a
Rhinorrhea	1.8 ± 3.1	0.8 ± 2.1	.264
Snoring	0.9 ± 3.3	0.7 ± 2.5	.848
Headache	1.8 ± 2.4	0.2 ± 1.9	.019^a
Facial pain	1.3 ± 2.3	−0.6 ± 2.1	.005^a
Olfactory change	1.6 ± 2.2	1.5 ± 3.1	.376
Modified Lund-Kennedy score	3.0 ± 2.0	2.5 ± 1.8	.510

Abbreviations: NOSE, Nasal Obstruction Symptoms Evaluation; SNOT-20, Sino-Nasal Outcome Test–20; VAS, visual analog scale.

P < .05.

Table 3.

Symptom Changes between the Xylitol and Saline Irrigation Treatments among Patients with Chronic Rhinosinusitis without Nasal Polyp Who Underwent Endoscopic Sinus Surgery (n = 8).

	Score Change, Mean ± SD		P Value
	Xylitol	Saline	P Value
NOSE	3.8 ± 9.0	3.6 ± 5.0	.798
SNOT-20	5.9 ± 12.0	5.8 ± 12.3	.798
VAS
Nasal stuffiness	1.8 ± 4.2	2.3 ± 3.6	>.99
Sneezing	1.0 ± 2.5	−0.9 ± 2.3	.721
Rhinorrhea	1.3 ± 1.5	−0.8 ± 2.1	.050
Snoring	0.1 ± 2.2	−0.1 ± 1.1	.959
Headache	0.3 ± 2.2	0.4 ± 0.7	.574
Facial pain	0.4 ± 2.6	1.5 ± 1.4	.382
Olfactory change	1.5 ± 2.3	0.5 ± 2.3	.505
Modified Lund-Kennedy score	2.4 ± 1.6	2.5 ± 1.8	.884

Abbreviations: NOSE, Nasal Obstruction Symptoms Evaluation; SNOT-20, Sino-Nasal Outcome Test–20; VAS, visual analog scale.

Table 4.

Symptom Changes between the Xylitol and Saline Irrigation Treatments among Patients Who Underwent Septoplasty (n = 39).

	Score Change, Mean ± SD		P Value
	Xylitol	Saline	P Value
NOSE	9.1 ± 8.9	7.9 ± 9.4	.597
SNOT-20	13.7 ± 16.7	14.1 ± 18.7	.929
VAS
Nasal stuffiness	9.6 ± 13.6	1.9 ± 2.8	.001^a
Sneezing	0.6 ± 2.1	0.6 ± 2.1	.957
Rhinorrhea	0.7 ± 2.6	1.6 ± 2.6	.101
Snoring	1.3 ± 2.5	1.3 ± 2.9	>.99
Headache	0.9 ± 2.3	0.8 ± 2.0	.915
Facial pain	1.1 ± 2.5	1.4 ± 2.3	.607
Olfactory change	1.7 ± 2.9	1.8 ± 3.2	.881

Abbreviations: NOSE, Nasal Obstruction Symptoms Evaluation; SNOT-20, Sino-Nasal Outcome Test–20; VAS, visual analog scale.

P < .05.

Table 5.

Symptom Changes between the Xylitol and Saline Irrigation Treatments among Patients Who Underwent Combined Surgery (n = 14).

	Score Change, Mean ± SD		P Value
	Xylitol	Saline	P Value
NOSE	10.6 ± 7.9	7.9 ± 9.7	.427
SNOT-20	14.0 ± 16.5	8.8 ± 22.6	.352
VAS
Nasal stuffiness	1.6 ± 3.8	2.1 ± 2.5	.603
Sneezing	1.3 ± 3.3	0.4 ± 1.7	.164
Rhinorrhea	1.6 ± 3.4	0.9 ± 2.5	.531
Snoring	0.1 ± 2.3	−0.4 ± 1.6	.427
Headache	0.6 ± 2.7	0.3 ± 3.2	.541
Facial pain	−0.5 ± 1.5	0.3 ± 2.9	.227
Olfactory change	1.1 ± 3.1	0.0 ± 2.4	.769
Modified Lund-Kennedy score	2.3 ± 1.9	2.5 ± 1.2	.603

Abbreviations: NOSE, Nasal Obstruction Symptoms Evaluation; SNOT-20, Sino-Nasal Outcome Test–20; VAS, visual analog scale.

Table 6.

Symptom Changes between the Xylitol and Saline Irrigation Treatments among Patients with Allergic Sensitization (n = 31).

	Score Change, Mean ± SD		P Value
	Xylitol	Saline	P Value
NOSE	8.6 ± 10.3	6.1 ± 9.8	.315
SNOT-20	13.1 ± 16.6	10.5 ± 20.1	.588
VAS
Nasal stuffiness	2.5 ± 3.9	1.5 ± 2.9	.241
Sneezing	0.5 ± 2.0	−0.1 ± 2.1	.238
Rhinorrhea	2.1 ± 2.4	0.8 ± 2.3	.024^a
Snoring	1.1 ± 2.1	0.7 ± 2.8	.575
Headache	0.9 ± 2.1	0.5 ± 1.9	.449
Facial pain	0.7 ± 1.7	0.7 ± 2.1	.948
Olfactory change	1.4 ± 2.9	1.5 ± 3.6	.845

Abbreviations: NOSE, Nasal Obstruction Symptoms Evaluation; SNOT-20, Sino-Nasal Outcome Test–20; VAS, visual analog scale.

P < .05.

The preference survey showed that more than half of the patients in each surgical group preferred xylitol irrigation (septoplasty, n = 22, 56.4%; ESS, n = 22, 64.7%; combined surgery, n = 8, 57.1%; Table 7 ). Regarding safety, no adverse events were reported during or after xylitol irrigation.

Table 7.

Patients’ Nasal Irrigation Preference.

	Patients, n (%)
	Xylitol	Isotonic Saline	Similar	Total
Septoplasty	22 (56.4)	5 (12.8)	12 (30.8)	39 (100)
ESS	22 (64.7)	5 (14.7)	1 (2.9)	34 (100)
Combined	8 (57.1)	1 (7.1)	5 (35.7)	14 (100)
All	52 (59.8)	11 (12.6)	24 (27.6)	87 (100)

Abbreviation: ESS, endoscopic sinus surgery.

Discussion

There have been several in vitro and in vivo studies on the antibacterial properties of xylitol. Zabner et al⁵ reported that the number of nasal coagulase-negative staphylococci significantly decreased after xylitol was sprayed into the nostril. Additionally, xylitol reduced the airway surface liquid salt concentration, thereby suppressing the effects of airway antimicrobial factors and augmenting the innate defense against microorganisms at the airway surface. Kontiokari et al showed that xylitol markedly reduced the growth of alpha-hemolytic streptococci, including Streptococcus pneumoniae.⁴ Brown et al reported that xylitol killed bacteria in a rabbit maxillary sinus model with Pseudomonas aeruginosa inoculation.³ Xylitol showed antiadhesive effects on epithelial cells in the context of the most common bacterial causes of rhinosinusitis (ie, S pneumoniae and Haemophilus influenzae).⁶ Xylitol also showed mucolytic effects on chronic rhinosinusitis mucus.¹⁶ A safety assessment was conducted with preclinical and clinical trials.¹⁷ In this context, xylitol irrigation showed good results in the ESS group in this study. However, in subanalysis, xylitol irrigation did not show significant superior results among patients with CRSwNP who received ESS, unlike patients with CRSsNP. Lots of studies reported different disease characters in CRSwNP as compared with CRSsNP. The limited role of antibiotics was well known,^18-20 and mucociliary function was changed in CRSwNP.²¹ Therefore, the different disease characters of CRSwNP might affect the result of xylitol irrigation.

Bacterial colonization is an important factor in rhinosinusitis and allergic rhinitis.²² A positive effect of xylitol solution on nasal congestion was demonstrated previously.²³ In this study, we further investigated the effect of xylitol irrigation of patients who had undergone septoplasty and subanalyzed a group of patients with allergic sensitization. For patients who underwent septoplasty, our study showed greater improvement in stuffiness in the xylitol irrigation group versus the saline group. Nasal stuffiness is one of the major postoperative complaints following septoplasty, so xylitol could be of overall benefit for septoplasty. Pastacaldi et al reported a close relationship among staphylococci, staphylococcal superantigens, and allergic respiratory diseases.²² In this context, xylitol irrigation might be more effective than saline irrigation for improving the rhinorrhea symptoms of patients with allergic sensitization. This study has a limitation in not stratifying beyond type of surgery. In this study, we focused on evaluating the effect of xylitol irrigation after surgery and did not stratify by indication for surgery. Further studies focusing on allergic rhinitis or other sinonasal diseases are needed to determine the clinical utility of xylitol.

For all assessments in this study, equivalent or superior outcomes were seen in the xylitol irrigation group as compared with the saline irrigation group. Patient preference could be an important factor when choosing a nasal irrigation solution.

Conclusion

In this study, we validated a previous study on xylitol nasal irrigation for patients who underwent ESS, by including a larger cohort. Xylitol irrigation is more effective for patients with CRSsNP, and it has a limited role in CRSwNP. Also, we found that xylitol nasal irrigation was useful in postoperative septoplasty care. For patients with allergic sensitization, rhinorrhea showed greater improvement in the xylitol group than in the saline group. In fact, all measured outcomes were equivalent or superior with xylitol irrigation versus saline irrigation. Patient preference is an important factor in the choice of a nasal irrigation solution.

Author Contributions

Do Hyun Kim, data analysis, drafting, final approval, and accountability for all aspects of the work; Yeonji Kim, data acquisition, revising it critically for important intellectual content, final approval, and accountability for all aspects of the work; Il Gye Lim, data acquisition, revising it critically for important intellectual content, final approval, and accountability for all aspects of the work; Jin Hee Cho, data acquisition, revising it critically for important intellectual content, final approval, and accountability for all aspects of the work; Yong Jin Park, data acquisition, revising it critically for important intellectual content, final approval, and accountability for all aspects of the work; Sung Won Kim, data acquisition, revising it critically for important intellectual content, final approval, and accountability for all aspects of the work; Soo Whan Kim, conception or design of the work, revising it critically for important intellectual content, final approval, and accountability for all aspects of the work.

Disclosures

Competing interests: None.

Sponsorships: None.

Funding source: This work was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education(2017R1D1A1B03027903), and the Bio & Medical Technology Development Program of the National Research Foundation(NRF) funded by the Ministry of Science & ICT(2018M3A9E8020856). The sponsors had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Footnotes

Acknowledgements

We thank Dr Hyeon Woo Yim (Department of Preventive Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea) for established crossover study design, calculated sample size, and statistical analysis.

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

References

Low

Woods

Ullah

Carney

AS.

A double-blind randomized controlled trial of normal saline, lactated Ringer’s, and hypertonic saline nasal irrigation solution after endoscopic sinus surgery. Am J Rhinol Allergy. 2014;28:225-231.

Suslu

Bajin

Suslu

Ogretmenoglu

Effects of buffered 2.3%, buffered 0.9%, and non-buffered 0.9% irrigation solutions on nasal mucosa after septoplasty. Eur Arch Otorhinolaryngol. 2009;266:685-689.

Brown

Graham

Cable

Ozer

Taft

Zabner

Xylitol enhances bacterial killing in the rabbit maxillary sinus. Laryngoscope. 2004;114:2021-2024.

Kontiokari

Uhari

Koskela

Effect of xylitol on growth of nasopharyngeal bacteria in vitro. Antimicrob Agents Chemother. 1995;39:1820-1823.

Zabner

Seiler

Launspach

et al . The osmolyte xylitol reduces the salt concentration of airway surface liquid and may enhance bacterial killing. Proc Natl Acad Sci U S A. 2000;97:11614-11619.

Kontiokari

Uhari

Koskela

Antiadhesive effects of xylitol on otopathogenic bacteria. J Antimicrob Chemother. 1998;41:563-565.

Weissman

Fernandez

Hwang

PH.

Xylitol nasal irrigation in the management of chronic rhinosinusitis: a pilot study. Laryngoscope. 2011;121:2468-2472.

Giotakis

Karow

Scheithauer

Weber

Riechelmann

Saline irrigations following sinus surgery—a controlled, single blinded, randomized trial. Rhinology. 2016;54:302-310.

Kim

Sung

Jung

et al . The effect of maxillary sinus irrigation on early prognostic factors after endoscopic sinus surgery: a preliminary study. Am J Rhinol Allergy. 2013;27:e158-e161.

10.

Wormald

Cain

Oates

Hawke

Wong

A comparative study of three methods of nasal irrigation. Laryngoscope. 2004;114:2224-2227.

11.

Yoo

Ference

Kuan

Lee

Wang

Suh

JD.

Evaluation of patient nasal saline irrigation practices following endoscopic sinus surgery. Int Forum Allergy Rhinol. 2018;8:32-40.

12.

Psaltis

Vaezeafshar

Cho

Hwang

PH.

Modification of the Lund-Kennedy endoscopic scoring system improves its reliability and correlation with patient-reported outcome measures. Laryngoscope. 2014;124:2216-2223.

13.

Stewart

Witsell

Smith

Weaver

Yueh

Hannley

MT.

Development and validation of the Nasal Obstruction Symptom Evaluation (NOSE) scale. Otolaryngol Head Neck Surg. 2004;130:157-163.

14.

Balaker

Bergsneider

Martin

Wang

MB.

Evolution of sinonasal symptoms following endoscopic anterior skull base surgery. Skull Base. 2010;20:245-251.

15.

Kim do

Hong

Jeun

et al . Anatomic changes caused by endoscopic endonasal transsphenoidal surgery and their effects on nasal functions. Otolaryngol Head Neck Surg. 2016;154:1132-1137.

16.

Hardcastle

Jain

Radcliff

et al . The in vitro mucolytic effect of xylitol and dornase alfa on chronic rhinosinusitis mucus. Int Forum Allergy Rhinol. 2017;7:889-896.

17.

Durairaj

Launspach

Watt

et al . Safety assessment of inhaled xylitol in mice and healthy volunteers. Respir Res. 2004;5:13.

18.

Korkmaz

Ocal

Tatar

et al . Biofilms in chronic rhinosinusitis with polyps: is eradication possible? Eur Arch Otorhinolaryngol. 2014;271:2695-2702.

19.

Schlosser

Soler

ZM.

Evidence-based treatment of chronic rhinosinusitis with nasal polyps. Am J Rhinol Allergy. 2013;27:461-466.

20.

Thomas

Alt

JA.

Oral therapeutics for rhinosinusitis with nasal polyposis. Adv Otorhinolaryngol. 2016;79:138-147.

21.

Chao

et al . Impairment of cilia architecture and ciliogenesis in hyperplastic nasal epithelium from nasal polyps. J Allergy Clin Immunol. 2014;134:1282-1292.

22.

Pastacaldi

Lewis

Howarth

Staphylococci and staphylococcal superantigens in asthma and rhinitis: a systematic review and meta-analysis. Allergy. 2011;66:549-555.

23.

Cingi

Birdane

Ural

Oghan

Bal

Comparison of nasal hyperosmolar xylitol and xylometazoline solutions on quality of life in patients with inferior turbinate hypertrophy secondary to nonallergic rhinitis. Int Forum Allergy Rhinol. 2014;4:475-479.